The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Regulation of α-Smooth Muscle Actin Expression in Granulation Tissue Myofibroblasts Is Dependent on the Intronic CArG Element and the Transforming Growth Factor-β1 Control Element
Open accessAbstract
Myofibroblasts are specialized contractile fibroblasts that are critical in wound closure and tissue contracture. Generation of contractile force is correlated with the expression of alpha-smooth muscle actin (alpha-SMA); however, little is known regarding molecular mechanisms that control activation of alpha-SMA in myofibroblasts in granulation tissue. The aims of the present studies were to identify sufficient promoter regions required for alpha-SMA expression in myofibroblasts in vivo and to determine whether activation of alpha-SMA expression in myofibroblasts in vivo is dependent on an intronic CArG [CC(A/T)6GG] and a transforming growth factor-beta1 control element (TCE) that are required for alpha-SMA expression in smooth muscle cells. A Lac Z transgene construct from -2600 through the first intron was expressed in myofibroblasts within granulation tissue of cutaneous wounds in a pattern that closely mimicked endogenous alpha-SMA expression. Mutation of either the intronic CArG element or the TCE completely inhibited transgene expression in myofibroblasts in granulation tissue and responsiveness to transforming growth factor-beta1 in cultured transgenic fibroblasts. These same elements were also critical in regulating alpha-SMA expression during skeletal muscle repair but not during skeletal muscle development. Taken together, these results provide the first in vivo evidence for the importance of the intronic CArG and TCE cis-elements in the regulation of alpha-SMA expression in myofibroblasts in granulation tissue.
Overview
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
Verification
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?
The transition from fibroblast to myofibroblast includes production of α-smooth muscle actin and its assembly into stress fibres.
“Phenotypic changes occurring in fibroblast-to-myofibroblast transition include the expression of the α-smooth muscle actin (α-SMA) and its incorporation into stress fibres that allows cell's migration and contraction [19,20].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Myofibroblasts and mechano-regulation of connective tissue remodelling
Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C., & Brown, R. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm809 · Cited by 4,290
Self-citationDesmoulière, A., Geinoz, A., Gabbiani, F., & Gabbiani, G. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.122.1.103 · Cited by 2,267
Manipulating the Mouse Embryo: A Laboratory Manual
Behringer, R. R., Gertsenstein, M., Nagy, K. V., & Nagy, A. (2002) · Cited by 2,046
Regulation of differentiation of vascular smooth muscle cells
Owens, G. K. (1995) · Physiological Reviews · doi:10.1152/physrev.1995.75.3.487 · Cited by 1,732
Self-citationSkalli, O., Ropraz, P., Trzeciak, A. M., Benzonana, G., Gillessen, D., & Gabbiani, G. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.103.6.2787 · Cited by 1,622
Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity
Hinz, B., Celetta, G., Tomasek, J. J., Gabbiani, G., & Chaponnier, C. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.9.2730 · Cited by 1,288
Self-citationDarby, I. A., Skalli, O., & Gabbiani, G. (1990) · PubMed · Cited by 1,180
Serini, G., Bochaton-Piallat, M.-L., Ropraz, P., Geinoz, A., Borsi, L., Zardi, L., & Gabbiani, G. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.3.873 · Cited by 847
Vaughan, M. B., Howard, E. W., & Tomasek, J. J. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4869 · Cited by 468
Self-citationMechanisms of force generation and transmission by myofibroblasts
Hinz, B., & Gabbiani, G. (2003) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2003.08.006 · Cited by 408
Du, K. L., Ip, H. S., Li, J., Chen, M., Dandré, F., Yu, W., Lu, M. M., Owens, G. K., & Parmacek, M. S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.7.2425-2437.2003 · Cited by 360
Self-citationLi, L., Miano, J. M., Mercer, B., & Olson, E. N. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.132.5.849 · Cited by 322
Hautmann, M. B., Madsen, C. S., & Owens, G. K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.16.10948 · Cited by 303
Self-citationSeparable Regulatory Elements Governing myogenin Transcription in Mouse Embryogenesis
Cheng, T.-C., Wallace, M., Merlie, J. P., & Olson, E. N. (1993) · Science · doi:10.1126/science.8392225 · Cited by 254
Mack, C. P., & Owens, G. K. (1999) · Circulation Research · doi:10.1161/01.res.84.7.852 · Cited by 243
Self-citationHinz, B., Gabbiani, G., & Chaponnier, C. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200201049 · Cited by 226
Mechanical Properties of the Extracellular Matrix Influence Fibronectin Fibril Assembly in Vitro
Halliday, N., & Tomasek, J. J. (1995) · Experimental Cell Research · doi:10.1006/excr.1995.1069 · Cited by 210
Self-citationJester, J. V., Huang, J., Petroll, W. M., & Cavanagh, H. D. (2002) · Experimental Eye Research · doi:10.1006/exer.2002.2066 · Cited by 209
α-Smooth muscle actin is transiently expressed in embryonic rat cardiac and skeletal muscles
Woodcock‐Mitchell, J., Mitchell, J. J., Low, R. B., Kieny, M., Sengel, P., Rubbia, L., Skalli, O., Jackson, B., & Gabbiani, G. (1988) · Differentiation · doi:10.1111/j.1432-0436.1988.tb00091.x · Cited by 190
Shimizu, R. T., Blank, R. S., Jervis, R., Lawrenz-Smith, S. C., & Owens, G. K. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7631 · Cited by 166
Self-citationCombinatorial Control of Smooth Muscle–Specific Gene Expression
Kumar, M. S., & Owens, G. K. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000065197.07635.ba · Cited by 164
Self-citationA role for serum response factor in coronary smooth muscle differentiation from proepicardial cells
Landerholm, T. E., Dong, X.-R., Lu, J., Belaguli, N. S., Schwartz, R. J., & Majesky, M. W. (1999) · Development · doi:10.1242/dev.126.10.2053 · Cited by 157
CArG elements control smooth muscle subtype–specific expression of smooth muscle myosin in vivo
Manabe, I., & Owens, G. K. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11385 · Cited by 142
Self-citation[28] Application of LacZ gene fusions to postimplantation development
Bonnerot, C., & Nicolas, J.-F. (1993) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(93)25031-v · Cited by 125
Hautmann, M. B., Adam, P. J., & Owens, G. K. (1999) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.19.9.2049 · Cited by 112
Self-citationMack, C. P., Thompson, M. M., Lawrenz-Smith, S. C., & Owens, G. K. (2000) · Circulation Research · doi:10.1161/01.res.86.2.221 · Cited by 109
Self-citationLiu, Y., Sinha, S., & Owens, G. K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301902200 · Cited by 107
Self-citationHasan, W., Zhang, R., Liu, M., Warn, J. D., & Smith, P. G. (2000) · Cell and Tissue Research · doi:10.1007/s004410000175 · Cited by 66
A Systematic Study of Wound Contraction in Mammalian Skin
Kennedy, D. F., & Cliff, W. J. (1979) · Pathology · doi:10.3109/00313027909061947 · Cited by 61
Yang, Y. F., Zhe, X., Phan, S. H., Ullenbruch, M., & Schuger, L. A. (2003) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2002-0315oc · Cited by 30
[27] Application of LacZ gene fusions to preimplantation development
Vernet, M., Bonnerot, C., Briand, P., et al. (1993) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(93)25030-6 · Cited by 29
Flagged first, then by citations
Cited by
Sorted by citations
Formation and function of the myofibroblast during tissue repair
Hinz, B. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700613 · Cited by 1,658
Frangogiannis, N. G. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvaa324 · Cited by 1,229
CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair
Willenborg, S., Lucas, T., van Loo, G., Knipper, J. A., Krieg, T., Haase, I., Brachvogel, B., Hammerschmidt, M., Nagy, A., Ferrara, N., et al. (2012) · Blood · doi:10.1182/blood-2012-01-403386 · Cited by 534
Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice
Deppermann, C., Cherpokova, D., Nurden, P., Schulz, J.-N., Thielmann, I., Kraft, P., Vögtle, T., Kleinschnitz, C., Dütting, S., Krohne, G., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69210 · Cited by 200
Velasquez, L. S., Sutherland, L. B., Liu, Z., Grinnell, F., Kamm, K. E., Schneider, J. W., Olson, E. N., & Small, E. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316764110 · Cited by 142
Charbonney, E., Speight, P., Masszi, A., Nakano, H., & Kapus, A. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-04-0335 · Cited by 84
Zoppi, N., Chiarelli, N., Binetti, S., Ritelli, M., & Colombi, M. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.01.005 · Cited by 49
Metadata
- Authors
- Tomasek, J. J., McRae, J., Owens, G. K., & Haaksma, C. J.
- Affiliations
- University of Oklahoma Health Sciences Center (US)
- University of Virginia (US)
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 166
- Issue
- 5
- Pages
- 1343-1351
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1606390
- OpenAlex
- W2090765436
- Cited by
- 101
- References
- 31
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 6 · 2014: 4 · 2013: 8 · 2012: 9
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01 HL38854, R01 GM060651, P01 HL19242)
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- alpha-smooth muscle actin, myofibroblasts, granulation tissue, CArG elements, cis-regulatory elements, promoter regulation, skin wound healing, skeletal muscle repair, smooth muscle cells
- MeSH terms
- Actins, Animals, Fibroblasts, Gene Expression Regulation, Genes, Regulator, Granulation Tissue, Introns, Male, Mice, Transgenic, Muscle, Smooth, Mutation, Promoter Regions, Genetic, Transforming Growth Factor beta, Genes, Reporter, Serum Response Factor, Myocytes, Smooth Muscle, Mice, Rats, Transforming Growth Factor beta1
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
