Firsthand cigarette smoke alters fibroblast migration and survival: Implications for impaired healing
Open accessAbstract
Although it is known that high levels of cigarette smoke lead to cell death, little is known about the effects of low‐to‐moderate levels of smoke components that are found in vivo, such as those experienced by cells in tissues. Clinical studies and experimental data show that smokers heal poorly and are more prone to develop fibrotic diseases. Here we show the effects of first‐hand cigarette smoke on fibroblasts, cells that are critically involved in these processes. Using doses of smoke found in the tissues of smokers and a variety of cell and molecular approaches, we show that these doses of cigarette smoke do not cause cell death but rather stimulate fibroblasts to produce stress response and survival proteins such as interleukin‐8, PKB/Akt, p53, and p21 that in turn contribute to an increase in cell survival. In addition, smoke‐treated cells show a decrease in cell migration, which can be explained by the increased cell adhesion and alterations in cytoskeletal elements. We also show that these levels of smoke cause changes in mitochondrial morphology with a minimum loss of function and these changes are the result of exposure to reactive oxygen species. We conclude that the increase in cell survival may lead to a build‐up of connective tissue in the area of a wound, potentially leading to delayed healing and/or fibrosis and that the alterations in the cytoskeleton and in cell adhesion result in inhibition of cell migration, a process that could lead to nonclosure of the wound for lack of proper fibroblast migration to form the healing tissue.
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Cigarette smoking inhibits fibroblast migration, which is essential for callus formation and, more generally, for an efficient healing process.
“Some researchers have suggested that cigarette smoking inhibits fibroblast migration, which is essential for callus formation and, more generally, for an efficient healing process [59].”
From Skeletal System Biology and Smoke Damage: From Basic Science to Medical Clinic (2021) · cites this paper as [59]
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Cites
The Role of Dynamin-Related Protein 1, a Mediator of Mitochondrial Fission, in Apoptosis
Frank, S., Gaume, B., Bergmann-Leitner, E. S., Leitner, W. W., Robert, E. G., Catez, F., Smith, C. L., & Youle, R. J. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00055-7 · Cited by 1,755 · see citing works
The myofibroblast in wound healing and fibrocontractive diseases
Gabbiani, G. (2003) · The Journal of Pathology · doi:10.1002/path.1427 · Cited by 1,630 · see citing works
The Molecular and Cellular Biology of Wound Repair
Clark, R. A. F., & Henson, P. M. (1988) · Springer eBooks · doi:10.1007/978-1-4615-1795-5 · Cited by 1,524 · see citing works
A Human Dynamin-related Protein Controls the Distribution of Mitochondria
Смирнова, Е. А., Shurland, D., Ryazantsev, S. N., & van der Bliek, A. M. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.2.351 · Cited by 734 · see citing works
The molecular and cellular biology of wound repair
Naylor, I. L. (1996) · British Journal of Plastic Surgery · doi:10.1016/s0007-1226(96)90047-8 · Cited by 668 · see citing works
Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers.
Russell, M. A., Jarvis, M., Iyer, R., & Feyerabend, C. (1980) · BMJ · doi:10.1136/bmj.280.6219.972 · Cited by 465 · see citing works
Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity.
PRYOR, W. A. (1997) · Environmental Health Perspectives · doi:10.1289/ehp.97105s4875 · Cited by 458 · see citing works
Li, Y., Dowbenko, D. J., & Lasky, L. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109062200 · Cited by 442 · see citing works
Wong, E. D., Wagner, J. A., Gorsich, S. W., McCaffery, J. M., Shaw, J. M., & Nunnari, J. M. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.2.341 · Cited by 356 · see citing works
The Effect of Cigarette Smoking on Skin-Flap Survival in the Face Lift Patient
Rees, T. D., Liverett, D. M., & Guy, C. L. (1984) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-198406000-00009 · Cited by 332 · see citing works
Pitts, K. R., Yoon, Y., Krueger, E. W., & McNiven, M. A. (1999) · Molecular Biology of the Cell · doi:10.1091/mbc.10.12.4403 · Cited by 311 · see citing works
Antioxidant responses to oxidant-mediated lung diseases
COMHAIR, S. A. A., & ERZURUM, S. C. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00491.2001 · Cited by 307 · see citing works
Absorption and metabolism of nicotine from cigarettes.
ARMITAGE, A. K., Dollery, C. T., George, C. F., Houseman, T. H., Lewis, P. J., & Turner, D. M. (1975) · BMJ · doi:10.1136/bmj.4.5992.313 · Cited by 293 · see citing works
Smoking as a risk factor for wound healing and infection in breast cancer surgery
Sørensen, L. T., Hørby, J., Friis, E., Pilsgaard, B., & Jørgensen, T. (2002) · European Journal of Surgical Oncology · doi:10.1053/ejso.2002.1308 · Cited by 276 · see citing works
A Critical Review of 300 Patients
Hartrampf, C. R., & Bennett, G. K. (1987) · Annals of Surgery · doi:10.1097/00000658-198705000-00009 · Cited by 275 · see citing works
Cigarette Smoking: Impairment of Digital Blood flow and Wound Healing in the Hand
Mosely, L. H., & FINSETH, F. J. (1977) · HAND · doi:10.1016/s0072-968x(77)80001-6 · Cited by 242 · see citing works
Yılmaz, S., Erçöçen, A. R., Can, Z., Yenıdünya, S., Edah, N., & Yormuk, E. (2001) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-200109150-00042 · Cited by 225 · see citing works
The pattern and mechanism of mitochondrial transport in axons
Hollenbeck, P. J. (1996) · Frontiers in bioscience · doi:10.2741/a118 · Cited by 219 · see citing works
Macrophages and fibroblasts express embryonic fibronectins during cutaneous wound healing.
Brown, L. F., Dubin, D. B., Lavigne, L. M., Logan, B., Dvorak, H. F., & Water, L. V. D. (1993) · PubMed Central · Cited by 192 · see citing works
NICOTINE AND ITS EFFECT ON WOUND HEALING
Mosely, L. H., FINSETH, F. J., & GOODY, M. (1978) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-197804000-00013 · Cited by 183 · see citing works
The Acute Effects of Cigarette Smoke Exposure on Experimental Skin Flaps
Nolan, J., Jenkins, R. A., Kurihara, K., et al. (1985) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-198504000-00018 · Cited by 180 · see citing works
Division of Mitochondria Requires a NovelDNM1-interacting Protein, Net2p
Cerveny, K. L., McCaffery, J. M., & Jensen, R. E. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.2.309 · Cited by 161 · see citing works
Kyerematen, G. A., & Vesell, E. S. (1991) · Drug Metabolism Reviews · doi:10.3109/03602539109029754 · Cited by 153 · see citing works
Riefkohl, R. E., Wolfe, J. A., Cox, E. B., & McCarty, K. S. (1986) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-198604000-00013 · Cited by 140 · see citing works
Knoll, M. F., & Talbot, P. (1998) · Reproductive Toxicology · doi:10.1016/s0890-6238(97)00100-7 · Cited by 115 · see citing works
Necrosis of Abdominoplasty and Other Secondary Flaps after TRAM Flap Breast Reconstruction
Kroll, S. S. (1994) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-199410000-00011 · Cited by 107 · see citing works
The effect of cigarette smoking on wound healing
Siana, J. E., Rex, S., & Gottrup, F. (1989) · Scandinavian Journal of Plastic and Reconstructive Surgery · doi:10.3109/02844318909075119 · Cited by 103 · see citing works
Cigarette smoking and coronary blood flow
Czernin, J. G., & Waldherr, C. (2003) · Progress in Cardiovascular Diseases · doi:10.1053/pcad.2003.00104 · Cited by 102 · see citing works
Cigarette smoking–associated elastotic changes in the skin
Boyd, A. S., Stasko, T., King, L. E., Cameron, G. S., Pearse, A. D., & Gaskell d, S. A. (1999) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(99)70400-7 · Cited by 101 · see citing works
Immediate Breast Reconstruction
Bailey, M. H., Smith, J. W., Casas, L. A., et al. (1989) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-198905000-00011 · Cited by 91 · see citing works
Feugate, J. E., Li, Q., Wong, L., & Martins‐Green, M. M. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200103062 · Cited by 88 · see citing works
Self-citationA physiologically based pharmacokinetic model for nicotine disposition in the Sprague-Dawley rat
Plowchalk, D. R., Andersen, M. E., & deBethizy, J. D. (1992) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(92)90297-6 · Cited by 87 · see citing works
Changes in the elastic tissue of the non-sun-exposed skin of cigarette smokers
Francès, C., Boisnic, S., Hartmann, D. J., Dautzenberg, B., Branchet, M., Charpentier, Y. L., & Robert, L. (1991) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1991.tb06037.x · Cited by 85 · see citing works
Divide and multiply: organelle partitioning in yeast
Catlett, N. L., & Weisman, L. S. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00124-1 · Cited by 83 · see citing works
p53-Dependent Induction of p21Cip1/WAF1/Sdi1 Protects against Oxygen-Induced Toxicity
Helt, C. E. (2001) · Toxicological Sciences · doi:10.1093/toxsci/63.2.214 · Cited by 79 · see citing works
Mitochondrial division: New partners in membrane pinching
Yoon, Y., & McNiven, M. A. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00011-2 · Cited by 69 · see citing works
Toenail nicotine levels as a biomarker of tobacco smoke exposure.
Al‐Delaimy, W. K., Mahoney, G. N., Speizer, F. E., & Willett, W. C. (2002) · PubMed · Cited by 51 · see citing works
Cigarette Smoke Produces Airway Wall Remodeling in Rat Tracheal Explants
Wang, R. D., Tai, H., Xie, C., et al. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200307-1006oc · Cited by 50 · see citing works
If You Continue To Smoke, We May Have a Problem: Smoking's Effects on Plastic Surgery
Aköz, T., Akan, M., & Yıldırım, S. (2002) · Aesthetic Plastic Surgery · doi:10.1007/s00266-002-2045-3 · Cited by 46 · see citing works
Kogan, M. J., Verebey, K., Jaffee, J., & Mulé, S. J. (1981) · Journal of Forensic Sciences · doi:10.1520/jfs11324j · Cited by 45 · see citing works
Vaingankar, S. M., & Martins‐Green, M. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.9.5226 · Cited by 41 · see citing works
Self-citationLi, Q.-J., Vaingankar, S. M., Sladek, F. M., & Martins‐Green, M. M. (2000) · Blood · doi:10.1182/blood.v96.12.3696 · Cited by 40 · see citing works
Self-citationThe unexplained survival of cells in oral cancer: what is the role of p53?
Whyte, D. A., Broton, C. E., & Shillitoe, E. J. (2002) · Journal of Oral Pathology and Medicine · doi:10.1034/j.1600-0714.2002._310301.x · Cited by 39 · see citing works
Tissue distribution of 63H9nicotine in dogs and rhesus monkeys*1
Tsujimoto, A. (1975) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(75)90191-x · Cited by 35 · see citing works
Feugate, J. E., Wong, L., Li, Q.-J., & Martins‐Green, M. M. (2002) · BMC Cell Biology · doi:10.1186/1471-2121-3-13 · Cited by 34 · see citing works
Self-citationNetscher, D. T. J., & Clamon, J. (1994) · Plastic and Aesthetic Nursing · doi:10.1097/00006527-199401440-00003 · Cited by 32 · see citing works
Cigarette Smoke: Effect of Aqueous and Nonaqueous Fractions on Mitochondrial Function
Gairola, C. G., & Aleem, M. (1973) · Nature · doi:10.1038/241287a0 · Cited by 22 · see citing works
NICOTINE IN BLOOD IN RELATION TO SMOKING
Wolff, W. A., Hawkins, M. A., & Giles, W. E. (1949) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)03522-0 · Cited by 18 · see citing works
Gh, O., Buyukcakir, C., & Fife, C. (2000) · PubMed · Cited by 15 · see citing works
Physiologically based pharmacokinetic modelling of nicotine
Schwartz, S. L., Gastonguay, M. R., Robinson, D. E., et al. (1993) · Springer eBooks · doi:10.1007/978-94-011-2110-1_12 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Krueger JK, Rohrich RJ. Clearing the smoke: the scientific ratio- nale for tobacco abstention with plastic surgery. Plast Reconstr Surg 2001;108:1063-73; discussion 1074-7.
- Netscher DT, Clamon J. Smoking: adverse effects on outcomes for plastic surgical patients. Plast Surg Nurs 1994;14:205-10.
Cited by
Sorted by citations
Sørensen, L. T., Toft, B. G., Rygaard, J., Ladelund, S., Paddon, M., James, T., Taylor, R., & Gottrup, F. (2010) · Surgery · doi:10.1016/j.surg.2010.02.005 · Cited by 117 · see citing works
Cigarette Smoke Induces Cellular Senescence via Werner's Syndrome Protein Down-regulation
Nyunoya, T., Monick, M. M., Klingelhutz, A. L., Glaser, H., Cagley, J. R., Brown, C. O., Matsumoto, E., Aykin-Burns, N., Spitz, D. R., Oshima, J., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200802-320oc · Cited by 79 · see citing works
Chang, C.-J., Jou, I.-M., Wu, T.-T., Su, F.-C., & Tai, T.-W. (2020) · Bone & Joint Research · doi:10.1302/2046-3758.93.bjr-2019-0089.r1 · Cited by 67 · see citing works
Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing
Dhall, S., Alamat, R., Castro, A., Sarker, A. H., Mao, J.-H., Chan, A., Hang, B., & Martins-Green, M. (2016) · Clinical Science · doi:10.1042/cs20160236 · Cited by 55 · see citing works
Self-citationSkeletal System Biology and Smoke Damage: From Basic Science to Medical Clinic
Tarantino, U., Cariati, I., Greggi, C., Gasbarra, E., Belluati, A., Ciolli, L., Maccauro, G., Momoli, A., Ripanti, S., Falez, F., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126629 · Cited by 52 · see citing works
- Authors
- Wong, L. S., & Martins‐Green, M.
- Affiliations
- University of California, Riverside (US)
- Corresponding author
- Martins‐Green, Manuela
- Venue
- Wound Repair and Regeneration
- Publisher
- Wiley
- Published
- 2004-07-19
- Volume
- 12
- Issue
- 4
- Pages
- 471-484
- ISSN
- 1067-1927 (ISSN-L)
- 1524-475X
- OpenAlex
- W2071859837
- Cited by
- 135
- References
- 50
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 9 · 2017: 4 · 2016: 8 · 2015: 7 · 2014: 9 · 2013: 7 · 2012: 7
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.escholarship.org
- Locations
- Wound Repair and Regeneration (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Heart Association
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- cigarette smoke, fibroblasts, fibroblast migration, cell survival, wound healing, fibrosis, interleukin-8, Akt signaling, p53, p21, cell adhesion, cytoskeleton, mitochondrial morphology, reactive oxygen species
- MeSH terms
- Cell Movement, Cell Survival, Fibroblasts, Flow Cytometry, Humans, Microtubules, Mitochondria, Smoking, Wound Healing, Immunoblotting
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