The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
α-Smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent TGFβ activation or collagen production across multiple models of organ fibrosis
Open accessAbstract
Fibrosis is a common pathological sequela of tissue injury or inflammation, and is a major cause of organ failure. Subsets of fibroblasts contribute to tissue fibrosis in multiple ways, including generating contractile force to activate integrin-bound, latent TGFβ and secreting excess amounts of collagens and other extracellular matrix proteins (ECM) that make up pathologic scar. However, the precise fibroblast subsets that drive fibrosis have been poorly understood. In the absence of well-characterized markers, α-smooth muscle actin (αSMA) is often used to identify pathologic fibroblasts, and some authors have equated αSMA+ cells with contractile myofibroblasts and proposed that these cells are the major source of ECM. Here, we investigated how well αSMA expression describes fibroblast subsets responsible for TGFβ activation and collagen production in three commonly used models of organ fibrosis that we previously reported could be inhibited by loss of αv integrins on all fibroblasts (using PDGFRβ-Cre). Interestingly, αSMA-directed deletion of αv integrins protected mice from CCl4-induced hepatic fibrosis, but not bleomycin-induced pulmonary or unilateral ureteral obstruction–induced renal fibrosis. Using Col-EGFP/αSMA-RFP dual reporter mice, we found that only a minority of collagen-producing cells coexpress αSMA in the fibrotic lung and kidney. Notably, Col-EGFP+αSMA-RFP− cells isolated from the fibrotic lung and kidney were equally capable of activating TGFβ as were Col-EGFP+αSMA-RFP+ cells from the same organ, and this TGFβ activation was blocked by a TGFβ-blocking antibody and an inhibitor of nonmuscle myosin, respectively. Taken together, our results suggest that αSMA is an inconsistent marker of contractile and collagen-producing fibroblasts in murine experimental models of organ fibrosis.
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A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
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Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix
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Latent TGF-β structure and activation
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Integrin–TGF‐β crosstalk in fibrosis, cancer and wound healing
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Self-citationThe α v β 1 integrin plays a critical in vivo role in tissue fibrosis
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Tsukui, T., Sun, K.-H., Wetter, J. B., Wilson-Kanamori, J. R., Hazelwood, L. A., Henderson, N. C., Adams, T. S., Schupp, J. C., Poli, S. D., Rosas, I. O., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15647-5 · Cited by 765
Self-citationSingle-Cell Deconvolution of Fibroblast Heterogeneity in Mouse Pulmonary Fibrosis
Xie, T., Wang, Y., Deng, N., Huang, G., Taghavifar, F., Geng, Y., Liu, N., Kulur, V., Yao, C., Chen, P., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.010 · Cited by 527
Zhang, T., Wang, X.-F., Wang, Z.-C., Lou, D., Fang, Q.-Q., Hu, Y.-Y., Zhao, W.-Y., Zhang, L.-Y., Wu, L.-H., & Tan, W.-Q. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110287 · Cited by 438
Jenkins, R. G., Moore, B. B., Chambers, R. C., Eickelberg, O., Königshoff, M., Kolb, M., Laurent, G. J., Nanthakumar, C. B., Olman, M. A., Pardo, A., et al. (2017) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2017-0096st · Cited by 435
Self-citationProgressive Pulmonary Fibrosis Is Caused by Elevated Mechanical Tension on Alveolar Stem Cells
Wu, H., Yu, Y., Huang, H., Hu, Y., Fu, S., Wang, Z., Shi, M., Zhao, X., Yuan, J., Li, J., et al. (2020) · Cell · doi:10.1016/j.cell.2019.11.027 · Cited by 417
Metadata
- Authors
- Sun, K.-H., Chang, Y., Reed, N. I., & Sheppard, D.
- Venue
- American Journal of Physiology-Lung Cellular and Molecular Physiology
- Publisher
- American Physiological Society
- Published
- 2016-05-01
- Volume
- 310
- Issue
- 9
- Pages
- L824-L836
- ISSN
- 1040-0605 (ISSN-L)
- 1522-1504
- OpenAlex
- W2288759932
- Cited by
- 198
- References
- 13
- FWCI
- 9.11
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: α-Smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent TGFβ activation or collagen production across multiple models of organ fibrosis. https://app.cochat.ai/papers/10.1152/ajplung.00350.2015
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- Sun, K.-H., Chang, Y., Reed, N. I., & Sheppard, D. (2016). α-Smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent TGFβ activation or collagen production across multiple models of organ fibrosis. American Journal of Physiology-Lung Cellular and Molecular Physiology. https://doi.org/10.1152/ajplung.00350.2015
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