Influence of Mast Cells in Drug-Induced Gingival Overgrowth
Open accessAbstract
Mast cells (MCs) are multifunctional effector cells that were originally thought to be involved in allergic disorders. Now it is known that they contain an array of mediators with a multitude of effects on many other cells. MCs have become a recent concern in drug-induced gingival overgrowth (DIGO), an unwanted outcome of systemic medication. Most of the studies have confirmed the significant presence of inflammation as a prerequisite for the overgrowth to occur. The inflammatory changes within the gingival tissue appear to influence the interaction between the inducing drug and the fibroblast activity. The development of antibodies to MC-specific enzymes, tryptase and chymase, has facilitated the study of mast cells in DIGO. Many immunohistochemical studies involving MCs have been conducted; as a result, DIGO tissues are found to have increased the number of MCs in the gingiva, especially in the area of fibrosis. At the cellular level, gingival fibrogenesis is initiated by several mediators which induce the recruitment of a large number of inflammatory cells, including MCs. The purpose of this paper is to access the roles played by MCs in gingival overgrowth to hypothesize a relationship between these highly specialized cells in the pathogenesis of DIGO.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There is a strong correlation between an increased plaque index and the severity of gingival overgrowth.
“Some authors report plaque elimination as a primary preventive measure for drug-induced gingival overgrowth, as there is a strong correlation between an increased plaque index and the severity of gingival overgrowth [10,11].”
From Sodium Valproate-Induced Gingival Enlargement in a Pediatric Patient: A Case Report With Surgical Intervention (2025) · cites this paper as [11]
The Introduction says gingival enlargement tends to be more severe where plaque accumulates, supporting an association. It does not report a plaque-index measurement or establish that the correlation is strong; it also does not identify plaque elimination as a primary preventive measure. No page number is available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Renin-angiotensin system: biochemistry and mechanisms of action.
Peach, M. J. (1977) · Physiological Reviews · doi:10.1152/physrev.1977.57.2.313 · Cited by 1,380 · see citing works
Marshall, J., & Bienenstock, J. (2004) · Springer Seminars in Immunopathology · doi:10.1007/bf00197505 · Cited by 1,307 · cited 3× · see citing works
“Importantly, in several models both MCT and MCTC were present and directly involved in gingival �brosis [8, 12].”
BackgroundEndothelin system: the double-edged sword in health and disease.
Kedzierski, R., & Yanagisawa, M. (2001) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.851 · Cited by 819 · cited 1× · see citing works
“Activation of both ETA and ETB on smooth muscle cells leads to vasoconstriction, whereas activation of ETB located on endothelial cells leads to vasodilation by increasing NO production [64].”
BackgroundPathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases.
Matsubara, H. (1998) · Circulation Research · doi:10.1161/01.res.83.12.1182 · Cited by 434 · cited 1× · see citing works
“Angiotensin II type 2 (AT2) receptors mediate vasodilatation, growth inhibition [27], and apoptosis [28].”
BackgroundThe pathogenesis of drug-induced gingival overgrowth.
Seymour, R., Thomason, J., & Ellis, J. (1996) · Journal of Clinical Periodontology · doi:10.1111/j.1600-051x.1996.tb02072.x · Cited by 432 · see citing works
Angiotensin-converting enzyme: new concepts concerning its biological role.
Ehlers, M., & Riordan, J. (1989) · Biochemistry · doi:10.1021/bi00439a001 · Cited by 395 · see citing works
Welle, M. (1997) · Journal of Leukocyte Biology · doi:10.1002/jlb.61.3.233 · Cited by 364 · see citing works
Tchougounova, E., Lundequist, A., Fajardo, I., Winberg, J., Åbrink, M., & Pejler, G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m410396200 · Cited by 344 · cited 1× · see citing works
“Studies using peritoneal mast cells isolated frommice have shown that chymase can activate MMP-2 and -9 [43].”
BackgroundRisk factors for drug‐induced gingival overgrowth
Seymour, R. A., Ellis, J. S., & Thomason, J. M. (2000) · Journal of Clinical Periodontology · doi:10.1034/j.1600-051x.2000.027004217.x · Cited by 310 · cited 3× · see citing works
“Prostaglandin Human gingival tissues, gingival �broblast, In�ammation, �broblast proliferation [1, 5, 54, 55]”
BackgroundProteolytic host cell enzymes in gingival crevice fluid.
Uitto, V., Overall, C., & McCulloch, C. (2003) · Periodontology 2000 · doi:10.1034/j.1600-0757.2003.03106.x · Cited by 272 · see citing works
History about the discovery of the renin-angiotensin system.
Basso, N., & Terragno, N. (2001) · HYPERTENSION · doi:10.1161/hy1201.101214 · Cited by 236 · see citing works
Hamblin, T. (1990) · British medical journal · doi:10.1136/bmj.301.6752.568 · Cited by 200 · cited 11×
“Moreover, mast cells are likely to contribute indirectly to the formation of endothelin by releasing chymase, which can generate ET-1, by cleavage of big ET-1 [61].”
BackgroundInfluentialMatsumoto, T., Wada, A., Tsutamoto, T., Ohnishi, M., Isono, T., & Kinoshita, M. (2003) · Circulation · doi:10.1161/01.cir.0000074041.81728.79 · Cited by 196 · see citing works
Mast cell population density, blood vessel density and histamine content in normal human skin
Eady, R., Cowen, T., Marshall, T. F., Plummer, V., & Greaves, M. (1979) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1979.tb08065.x · Cited by 184 · cited 1× · see citing works
“ey locate close to blood vessels, epithelia, and nerves in connective tissues, allowing their input in homeostatic functions and also being primary immune barriers [9, 10].”
BackgroundMast cells: a unique source of renin.
Silver, R., Reid, A., Mackins, C. J., Askwith, T., Schaefer, U., Herzlinger, D., & Levi, R. (2004) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0403208101 · Cited by 182 · cited 1× · see citing works
“Mast cells synthesize renin and release during degranulation that can generate Ang II from Ang I [21, 30].”
BackgroundA clinical review of drug-induced gingival overgrowths.
Marshall, R., & Bartold, P. (1999) · Australian dental journal · doi:10.1111/j.1834-7819.1999.tb00224.x · Cited by 180 · see citing works
LEES, M., TAYLOR, D. J., & WOOLLEY, D. E. (1994) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1994.tb18980.x · Cited by 178 · cited 2× · see citing works
“Studies linking peritoneal and skinmast cells to tissue remodelling have shown that mast cell tryptase can activate interstitial collagenase (MMP-1) and stromelysin (MMP-3) under in vitro conditions [41, 42].”
BackgroundM ast C ells and O ral I nflammation
Walsh, L. J. (2003) · Critical Reviews in Oral Biology & Medicine · doi:10.1177/154411130301400304 · Cited by 176 · see citing works
The prevalence and severity of cyclosporin and nifedipine-induced gingival overgrowth.
Thomason, J., Seymour, R. A., & Rice, N. (1993) · Journal of Clinical Periodontology · doi:10.1111/j.1600-051x.1993.tb01757.x · Cited by 174 · see citing works
Cell biology and genetics of angiotensin in cardiovascular disease
Dzau, V. (1994) · Journal of Hypertension - Supplement · doi:10.1097/00004872-199407030-00002 · Cited by 173 · see citing works
Gómez-Garre, D., Ruiz-Ortega, M., Ortego, M., Largo, R., López-Armada, M., Plaza, J., González, E., & Egido, J. (1996) · HYPERTENSION · doi:10.1161/01.hyp.27.4.885 · Cited by 166 · cited 2× · see citing works
“In addition, growing evidence from other tissues suggests that ET-1 induces the expression of many types of MMPs as well as ECM protein expression, including collagens, laminin, and �bronectin (FN), in cell culture and animal models [39, 45].”
BackgroundC onnective T issue M etabolism and G ingival O vergrowth
Trackman, P. C., & Kantarcı, A. (2004) · Critical Reviews in Oral Biology & Medicine · doi:10.1177/154411130401500305 · Cited by 153 · see citing works
Connective Tissue Growth Factor in Drug‐Induced Gingival Overgrowth
Uzel, M. I., Kantarci, A., Hong, H., Uygur, C., Sheff, M. C., Firatli, E., & Trackman, P. C. (2001) · Journal of Periodontology · doi:10.1902/jop.2001.72.7.921 · Cited by 150 · cited 2× · see citing works
“CSF, GM-CSF Human gingival �broblast, human gingival tissues Fibroblast proliferation, collagen synthesis, cytokine generation [13, 50, 51]”
BackgroundAngiotensin II stimulates endothelin-1 secretion in cultured rat mesangial cells
Kohno, M., Horio, T., Ikeda, M., Yokokawa, K., Fukui, T., Yasunari, K., Kurihara, N., Takeda, T., & Johchi, M. (1992) · Kidney International · doi:10.1038/ki.1992.361 · Cited by 138 · cited 1× · see citing works
“ET-1 was produced by cultured endothelial cells and MCs aer Ang II stimulation [67, 68].”
BackgroundMatrix Metalloproteinases: Pathways of Induction by Bioactive Molecules
Tsuruda, T., Costello-Boerrigter, L., & Burnett, J. (2004) · Heart Failure Reviews · doi:10.1023/b:hrev.0000011394.34355.bb · Cited by 135 · see citing works
Artuc, M., Steckelings, U. M., & Henz, B. M. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01705.x · Cited by 134 · see citing works
Kokkonen, J., Saarinen, J., & Kovanen, P. T. (1997) · Circulation · doi:10.1161/01.cir.95.6.1455 · Cited by 131 · see citing works
Kawaguchi, H., Sawa, H., & Yasuda, H. (1990) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(90)90115-i · Cited by 115 · cited 1× · see citing works
“On the other hand, ET-1 enhanced the conversion of Ang I to Ang II in pulmonary artery endothelial cells [70].”
BackgroundRegulation of endothelin-1 mRNA by angiotensin II in rat heart endothelial cells.
Chua, B., Chu, C.-C., Diglio, C., & Siu, B. (1993) · Biochimica et Biophysica Acta · doi:10.1016/0167-4889(93)90010-m · Cited by 108 · cited 1× · see citing works
“ET-1 was produced by cultured endothelial cells and MCs aer Ang II stimulation [67, 68].”
BackgroundMolecular and cellular mechanism of angiotensin II-mediated apoptosis.
Horiuchi, M., Akishita, M., & Dzau, V. (1998) · Endocrine Research · doi:10.3109/07435809809032610 · Cited by 104 · cited 1× · see citing works
“In its target cells, Ang II binds to different subtypes of G protein-coupled receptors and induces constriction [25], hypertrophy, and proliferation [26] via the angiotensin II type 1 (AT1) receptor.”
BackgroundEndothelin modulates angiotensin II-induced mitogenesis of human mesangial cells.
Bakris, G., & Ré, R. (1993) · American Journal of Physiology · doi:10.1152/ajprenal.1993.264.6.f937 · Cited by 96 · cited 1×
“Furthermore, Ang II increases the production of ET-1 by human MCs and subsequently contributes to its mitogenic effects [69].”
BackgroundSuzuki, K., Martyn, L. E. E. S., Newlands, G. F. J., Nagase, H., & Woolley, D. E. (1995) · Biochemical Journal · doi:10.1042/bj3050301 · Cited by 92 · see citing works
Drug-induced gingival overgrowth.
Dongari, A., McDonnell, H. T., & Langlais, R. (1993) · Oral surgery, oral medicine, and oral pathology · doi:10.1016/0030-4220(93)90027-2 · Cited by 83 · see citing works
Quantification of mast cells in different stages of human periodontal disease.
Batista, A., Rodini, C., & Lara, V. (2005) · Oral Diseases · doi:10.1111/j.1601-0825.2005.01113.x · Cited by 82 · cited 1×
“…is initiated by several mediators which induce the recruitment of a large number of in�ammatory cells, including MCs. e purpose of this paper is to access the roles played by MCs in gingival overgrowth to hypothesize a relationship between these highly specialized cells in the pathogenesis of DIGO.”
BackgroundMast cell infiltration and chemokine expression in progressive renal disease.
Jones, S. E. F., Kelly, D., Cox, A., Zhang, Y., Gow, R., & Gilbert, R. (2003) · Kidney International · doi:10.1046/j.1523-1755.2003.00183.x · Cited by 77 · see citing works
Mast cells--a role in periodontal diseases?
Steinsvoll, S., Helgeland, K., & Schenck, K. (2004) · Journal of Clinical Periodontology · doi:10.1111/j.1600-051x.2004.00516.x · Cited by 74 · cited 1× · see citing works
“Prostaglandin Human gingival tissues, gingival �broblast, In�ammation, �broblast proliferation [1, 5, 54, 55]”
BackgroundMechanisms of activation of human mast cells and basophils by general anesthetic drugs.
Marone, G., Stellato, C., Mastronardi, P., & Mazzarella, B. (1993) · Annales Francaise d'Anesthesie et de Reanimation · doi:10.1016/s0750-7658(05)81020-2 · Cited by 74 · see citing works
Tryptase and chymase, markers of distinct types of human mast cells
Craig, S. S., & Schwartz, L. B. (1989) · Immunologic Research · doi:10.1007/bf02919075 · Cited by 74 · cited 1× · see citing works
“Tryptase Human gingival �broblast, human gingival tissues �broblast proliferation, in�ammation [8, 41, 42, 48, 49]”
BackgroundFraccarollo, D., Galuppo, P., Bauersachs, J. K., & Ertl, G. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00256-0 · Cited by 68 · see citing works
Atilla, G., & Kütükçüler, N. (1998) · The Journal of Periodontology · doi:10.1902/jop.1998.69.7.784 · Cited by 68 · see citing works
Non-anticoagulant Effects of Heparin: An Overview
Lever, R., & Page, C. P. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-23056-1_12 · Cited by 63 · see citing works
Riekki, R., Harvima, I., Jukkola, A., Risteli, J., & Oikarinen, A. (2004) · Experimental Dermatology · doi:10.1111/j.0906-6705.2004.00164.x · Cited by 62
Mariani, G., Calastrini, C., Carinci, F., Bergamini, L., Calastrini, F., & Stabellini, G. (1996) · The Journal of Periodontology · doi:10.1902/jop.1996.67.1.21 · Cited by 45 · cited 3× · see citing works
“Mariani et al., 1996, examined the overgrowth that affected gingiva of patients treated with cyclosporine aer kidney transplant to evaluate the involvement of connective tissue [6]. e ultrastructural study showed that the dimensional increase was largely due to increased production of amorphous…”
BackgroundInfluentialAlternative pathways for angiotensin II generation in the cardiovascular system.
Becari, C., Oliveira, E., & Salgado, M. C. O. (2011) · Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · doi:10.1590/s0100-879x2011007500093 · Cited by 40 · cited 3×
“e accumulating evidence demonstrated the alternative Ang II-generating pathway through the enzyme mast cell chymase [29].”
BackgroundNorrby, K. (1997) · Inflammation Research · doi:10.1007/pl00022372 · Cited by 40 · cited 11×
“TGF-ββ Human gingival �broblast, human gingival tissues Collagen synthesis, �bronectin generation, reduce MMP-1 synthesis [13, 31, 32, 34]”
BackgroundInfluentialOhuchi, N., Koike, K., Sano, M., Kusama, T., Kizawa, Y., Hayashi, K., Taniguchi, Y., Ohsawa, M., Iwamoto, K., & Murakami, H. (2002) · Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · doi:10.1016/s1532-0456(02)00098-4 · Cited by 37
Expression of endothelin-1 in gingival epithelial cells.
Yamamoto, E., Awano, S., Koseki, T., Ansai, T., & Takehara, T. (2003) · Journal of Periodontal Research · doi:10.1034/j.1600-0765.2003.00668.x · Cited by 36 · cited 1×
“ere are currently two distinct human endothelin receptors known, ETA andETB,which aremembers of the seven transmembrane G protein-coupled rhodopsin superfamily [62, 63].”
BackgroundSantos, P. P. D. A., Nonaka, C., Pinto, L., & de Souza, L. D. (2011) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2010.09.020 · Cited by 35
Increased bFGF level in the serum of patients with phenytoin-induced gingival overgrowth.
Sasaki, T., & Maita, E. (1998) · Journal of Clinical Periodontology · doi:10.1111/j.1600-051x.1998.tb02362.x · Cited by 32 · cited 3× · see citing works
“b-FGF Human gingival �brobalsts, gingival tissues Fibroblast proliferation [50]”
BackgroundHigh-turnover osteoporosis is induced by cyclosporin A in rats
Wada, C., Kataoka, M., Seto, H., Hayashi, N., Kido, J., Shinohara, Y., & Nagata, T. (2006) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-005-0672-x · Cited by 30 · cited 1× · see citing works
“Corticotropin releasing factor, Endorphins, Somatostatin Human gingival tissues and crevicular �uid, Rat oral tissues Vasodilatation, analgesia, in�ammation [38, 53, 54]”
BackgroundExpression of endothelins and their receptors in cells from human periodontal tissues.
Fujioka, D., Nakamura, S., Yoshino, H., Shinohara, H., Shiba, H., Mizuno, N., Hasegawa, N., Shindoh, N., Uchida, Y., Ogawa, T., et al. (2003) · Journal of Periodontal Research · doi:10.1034/j.1600-0765.2003.00653.x · Cited by 30 · cited 1× · see citing works
“ere are currently two distinct human endothelin receptors known, ETA andETB,which aremembers of the seven transmembrane G protein-coupled rhodopsin superfamily [62, 63].”
BackgroundMast cells and fibroblasts: two interacting cells
Rubinchik, E., & Levi-Schaffer, F. (1994) · International journal of clinical & laboratory research (Print) · doi:10.1007/bf02592443 · Cited by 28
Sano, M., Ohuchi, N., Inoue, T., Tono, K., Tachikawa, T., Kizawa, Y., & Murakami, H. (2004) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2004.00257.x · Cited by 20 · see citing works
Thrombin‐stimulated proliferation is mediated by endothelin‐1 in cultured rat gingival fibroblasts
Ohuchi, N., Hayashi, K., Iwamoto, K., Koike, K., Kizawa, Y., Nukaga, M., Kakegawa, T., & Murakami, H. (2009) · Fundamental & Clinical Pharmacology · doi:10.1111/j.1472-8206.2009.00786.x · Cited by 18
Crevicular fluid endothelin-1 levels in periodontal health and disease.
Pradeep, A., Guruprasad, C., Swati, P., & Shikha, C. (2008) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.2007.01026.x · Cited by 17 · see citing works
Fildes, J., Walker, A. H., Keevil, B., Hutchinson, I., Leonard, C., & Yonan, N. (2004) · Transplantation Proceedings · doi:10.1016/j.transproceed.2005.10.099 · Cited by 16 · see citing works
Endothelin-1 and Its Receptors ETA and ETB in Drug-Induced Gingival Overgrowth.
Tamilselvan, S., Raju, S. N., Loganathan, D., Kamatchiammal, S., Abraham, G., & Suresh, R. (2007) · The Journal of Periodontology · doi:10.1902/jop.2007.060172 · Cited by 15
Nurmenniemi, P., Pernu, H., & Knuuttila, M. (2004) · The Journal of Periodontology · doi:10.1902/jop.2004.75.7.933 · Cited by 15 · cited 6×
“level, gingival �brogenesis is initiated by several mediators which induce the recruitment of a large number of in�ammatory cells, including mast cells (MCs) [8].”
BackgroundInfluentialSoory, M., & Suchak, A. (2001) · Archives of Oral Biology · doi:10.1016/s0003-9969(01)00037-1 · Cited by 14 · see citing works
Buduneli̇, N., Sağol, Ö., Atilla, G., Duman, S., & Holmstrup, P. (2001) · Acta Odontologica Scandinavica · doi:10.1080/000163501317153211 · Cited by 14 · cited 1×
“Histamine Human gingival �broblast, skin �broblast Fibroblast proliferation and collagen synthesis [17, 35, 36]”
BackgroundSerotonin in rat oral tissues: role of 5-HT1 receptors in sympathetic vascular control.
Kerezoudis, N., Nomikos, G., Olgart, L., & Svensson, T. (1995) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)00772-y · Cited by 13 · cited 3×
“Vasodilatation Vasoconstriction [3, 53, 54, 56] Prostaglandin Human gingival tissues,gingival �broblast, In�ammation, �broblast proliferation [1, 5, 54, 55] Nitric Oxide Crevicular �uid from DIGO developed patients, human gingival tissues Vasodilatation, neurotransmission [4, 5, 57] IL-1, 2, 3, 4, 5, 6, 8, 9, 10, 13,…”
Expression of TNF-α and RANTES in drug-induced human gingival overgrowth
Subramani, T., Dhanaraj, L., Senthilkumar, K., Periasamy, S., Abraham, G., & Rao, S. (2010) · Indian Journal of Pharmacology · doi:10.4103/0253-7613.66842 · Cited by 10
Self-citationAsahara, Y., Nishimura, F., Yamada, H., Naruishi, K., Kataoka, M., Kido, J., Nagata, T., & Murayama, Y. (2000) · The Journal of Periodontology · doi:10.1902/jop.2000.71.7.1117 · Cited by 8 · cited 1×
“In contrast to this, Asahara et al., 2000, demonstrated that mast cells are not necessary in the development of cyclosporin A-induced gingival hyperplasia, and that the increased number of mast cell observed in the enlarged gingiva may be a secondary effect of gingival hyperplasia [72].”
ResultKatada, J., Muramatsu, M., Hayashi, M., & Hattori, M. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00422-7 · Cited by 5 · cited 1×
“Mast cells synthesize renin and release during degranulation that can generate Ang II from Ang I [21, 30].”
BackgroundPhagocytosis of mast cell granules by fibroblasts of the human gingiva
Takeda, Y. (2004) · Virchows Archiv · doi:10.1007/bf00737085 · Cited by 5
Gordon, H. A., Rovin, S., & Bruckner, G. (1978) · Gerontology · doi:10.1159/000212231 · Cited by 4
Flagged first, then by citations
11 of the 77 references couldn’t be matched to a known paper.
Research works printed but not linked: 13
- [12]Metcalfe DD Baram D Mekori YA Mast cells Physiological Reviews 1997 77 4 1033 1079 2-s2.0-0030772226 9354811
- [15]Marks RM Roche WR Czerniecki M Mast cell granules cause proliferation of human microvascular endothelial cells Laboratory Investigation 1986 55 3 289 294 2-s2.0-0022547395 2427796
- [17]Zhao ZZ Sugerman PB Zhou XJ Walsh LJ Savage NW Oral and maxillofacial pathology: mast cell degranulation and the role of T cell RANTES in oral lichen planus Oral Diseases 2001 7 4 246 251 2-s2.0-0035404819 11575876
- [18]Di Girolamo N Wakefield D In vitro and in vivo expression of interstitial collagenase/MMP-1 by human mast cells Developmental Immunology 2000 7 2-4 131 142 2-s2.0-0033777688 11097207 PMC2276052
- [31]Swales JD Samani NJ Localisation and physiological effects of tissue renin-angiotensin systems Journal of Human Hypertension 1989 3 1 71 77 2-s2.0-0024348339 2674444
- [32]Skidgel RA Schulz WW Tam LT Erdos EG Human renal angiotensin I converting enzymeand neutral endopeptidase Kidney International 1987 31 20 S45 S48 2-s2.0-0023278590 3037174
- [34]Ohuchi N Taniguchi Y Hayashi K Contribution of TGF-ALPHA to EGF receptor transactivation leading to proliferative response of rabbit gingival fibroblasts to angiotensin II and endothelin-1 Journal of Pharmacological Science 2006 100 supplement 1 1 p. 271P
- [38]Pihlstrom BL Michalowicz BS Johnson NW Periodontal diseases Lancet 2005 366 9499 1809 1820 2-s2.0-27844502483 16298220
- [45]Fraccarollo D Galuppo P Bauersachs J Ertl G Collagen accumulation after myocardial infarction: effects of ETA receptor blockade and implications for early remodeling Cardiovascular Research 2002 54 3 559 567 2-s2.0-0036272196 12031701
- [47]Hattori T Ara T Wang P Participation of tyrosine kinase and phospholipase Cγ in isradipine-induced proliferation of cultured human gingival fibroblasts European Journal of Medical Research 2005 10 12 543 546 2-s2.0-29444446809 16356872
- [54]Walsh LJ Mast cells and oral inflammation Critical Reviews in Oral Biology and Medicine 2003 14 3 188 198 2-s2.0-0038544209 12799322
- [56]Trackman PC Kantarci A Connective tissue metabolism and gingival overgrowth Critical Reviews in Oral Biology and Medicine 2004 15 3 165 175 2-s2.0-3042702736 15187034
- [61]Levin ER Endothelins New England Journal of Medicine 1995 333 6 356 363 2-s2.0-0029116310 7609754
Cited by
Sorted by citations
Drug-induced gingival overgrowth: the nemesis of gingiva unravelled
Bharti, V., & Bansal, C. (2013) · Journal of Indian Society of Periodontology · doi:10.4103/0972-124x.113066 · Cited by 88 · see citing works
“[20,21] Recently, Subramani et al ., [22] observed that mast cells participate in many inflammatory oral diseases, particularly those associated with fibrosis.”
The Role of Immune Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis
Xu, Y., Lan, P., & Wang, T. (2023) · Medicina · doi:10.3390/medicina59111984 · Cited by 57 · see citing works
Sheethal, H., Kn, H., Smitha, T., & Chauhan, K. (2018) · Journal of Oral and Maxillofacial Pathology · doi:10.4103/jomfp.jomfp_278_17 · Cited by 20
“On the whole, the cyclic activity of inflammatory mediator secretion and MC degranulation may result in the chronicity of gingival inflammation and fibrosis.[27] Role of mast cells in collagen synthesis and fibrosis MC‐derived IL‐1 causes increased fibroblastic response and tryptase causes increased production of Type…”
BackgroundRefining the Mechanism of Drug-Influenced Gingival Enlargement and Its Management
Sabarudin, M. A., Taib, H., & Mohamad, W. M. W. (2022) · Cureus · doi:10.7759/cureus.25009 · Cited by 19 · see citing works
Nonsurgical Management of Nifedipine Induced Gingival Overgrowth
Sam, G., & Sebastián, S. (2014) · Case Reports in Dentistry · doi:10.1155/2014/741402 · Cited by 13 · see citing works
“Upon their activation, they promote the local renin angiotensin system generation consequently able to stimulate endothelin and other profibrotic mediators [13].”
BackgroundLi, W.-Y., Wu, C.-H., Yang, J., Tang, M., Chen, L.-J., & Zhao, S.-L. (2015) · Inflammation · doi:10.1007/s10753-015-0126-0 · Cited by 12
Phenytoin-induced gingival overgrowth caused by death receptor pathway malfunction.
Takeuchi, R., Matsumoto, H., Arikawa, K., Taguchi, C., Nakayama, R., Nasu, I., & Hiratsuka, K. (2017) · Oral Diseases · doi:10.1111/odi.12651 · Cited by 11 · see citing works
Cellular crosstalk mechanism of Toll-like receptors in gingival overgrowth (Review)
Subramani, T., Rathnavelu, V., Alitheen, N. B., & Padmanabhan, P. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2144 · Cited by 15 · see citing works
“The reduction in cell signaling induced by drugs such as phenytoin may alter the inflammatory response in gingival tissues, favoring bacterial invasion and proliferation and, therefore, may be an important factor in the pathogenesis of gingival fibrosis (48).”
Self-citationAsif, S., Shaik, N., Barthunia, B., Kaleem, S., Zakirulla, M., Kota, M. Z., & Baig, F. (2018) · BMC Oral Health · doi:10.1186/s12903-018-0690-4 · Cited by 10 · see citing works
“Evidence from animal studies confirms that, nifedipine when added to gingival fibroblast in culture, increase the conversion of testosterone to 5α dihydrotestosterone and this active metabolite would target subpopulations of fibroblasts [12, 13].”
Al-hamilly, N. S., Radwan, L. R. S., Abdul-Rahman, M., Mourad, M. I., & Grawish, M. (2016) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2016.02.006 · Cited by 10
Polypharmacy and Oral Health among the Elderly
Doğan, M. S. (2016) · Journal of Dentistry Oral Disorders and Therapy · doi:10.15226/jdodt.2016.00151 · Cited by 2 · see citing works
Missing diagnosis: gingival hypertrophy due to amlodipine.
Tomar, L., & Aggarwal, A. (2015) · Indian Heart Journal · doi:10.1016/j.ihj.2015.06.011 · Cited by 4
“Gingival hypertrophy due to drugs is termed as ‘‘drug-induced gingival overgrowth (DIGO)’’.(1) Drugs that cause GH are: anticonvulsants such as phenytoin, phenobarbital, lamotrigine, valproate, vigabatrin, ethosuximide, topiramate, primidone; and calcium channel blockers such as nifedipine, amlodipine, verapamil, nife…”
BackgroundErtugrul, T., Tütüncü, Ş., Delice, N., & Özdemir, B. (2024) · Anatomia, Histologia, Embryologia. Journal of Veterinary Medicine Series C · doi:10.1111/ahe.13069 · Cited by 2 · see citing works
“These cells have also been observed to be consistently present in the healthy connective tissue of the gingiva (Subramani et al., 2013).”
Takeuchi, R., Matsumoto, H., Taguchi, C., Okada, Y., Mizuta, M., Yamada, T., Aso, T., Sakazume, H., Arikawa, K., & Hiratsuka, K. (2021) · International Journal of Oral-Medical Sciences · doi:10.5466/ijoms.20.109 · Cited by 2
Varghese, N., Rajesh, R., Krishnan, D., & Vasu, S. (2025) · Cureus · doi:10.7759/cureus.86519 · Cited by 1 · see citing works
“Some authors report plaque elimination as a primary preventive measure for drug-induced gingival overgrowth, as there is a strong correlation between an increased plaque index and the severity of gingival overgrowth [10,11].”
Amlodipine-induced reversible gum hypertrophy
Manish, G., Shobhit, S., Sukriti, K., Bhattacharjee, A., & Singh, R. (2016) · doi:10.4103/2045-080x.186175 · Cited by 1
“Gingival fibroblasts are stimulated by several mediators, including mast cells,[7] resulting in recruitment of a large number of inflammatory cells.”
BackgroundSubramani, T., Senthilkumar, K., & Periasamy, S. (2013) · doi:10.1155/2013/812842 · Cited by 1
“The release of these substances from MCs in inflammatory lesions is thought to play an important role in acceleration of the inflammatory process, angiogenesis, and fibrosis [2, 3].”
BackgroundSelf-citationAlesawy, A., Alotaibi, N., Alalshaikh, M., Aljofi, F. E., Al-Dossary, N., Al-Zahrani, N., Omar, O., & Madi, M. (2025) · PeerJ · doi:10.7717/peerj.19102
“However, studies have shown that phenytoin treatment is frequently associated with fibrotic drug-induced gingival overgrowth ( Subramani et al., 2013 ).”
Role of CD117 and mast cells in periodontal diseases: Histological and immunohistochemical study
Khaphi, F. L., Hussein, H., Hameed, O., Jebur, H., & Saeed, Z. (2025) · Journal of Advanced Biotechnology and Experimental Therapeutics · doi:10.5455/jabet.2025.15
“However, it is sensitive to physical factors such as metal ions or laser radiation (low-intensity) [14, 15].”
Prevalence of Gingival Hyperplasia Secondary to Amlodipine
Kalburgi, V., Raghuwanshi, S., Lavanya, N., Singh, M., & Raghuwanshi, S. (2015) · doi:10.5866/2015.7.10168
- Authors
- Subramani, T., Rathnavelu, V., Yeap, S. K., & Alitheen, N. B.
- Affiliations
- Universiti Putra Malaysia (MY)
- Sri Ramachandra Institute of Higher Education and Research (IN)
- Corresponding author
- Alitheen, Noorjahan Banu
- Venue
- Mediators of Inflammation
- Publisher
- Wiley
- Published
- 2013
- Volume
- 2013
- Pages
- 1-8
- ISSN
- 0962-9351 (ISSN-L)
- 1466-1861
- PMC
- PMC3569901
- OpenAlex
- W2019157311
- Cited by
- 24
- References
- 77
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 5 · 2014: 2 · 2013: 2
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Mediators of Inflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Universiti Putra Malaysia Institutional Repository (Universiti Putra Malaysia) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Health Professions › Pharmacy › Oral and gingival health research
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- mast cells, drug-induced gingival hyperplasia, gingivitis, gingival fibroblasts, tryptase, chymase, mast cell mediators, gingival fibrosis, pathogenesis, immunohistochemistry
- MeSH terms
- Fibrosis, Humans, Mast Cells, Gingival Overgrowth, Tryptases, Chymases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
