| First Author | Sun KH | Year | 2016 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 310 |
| Issue | 9 | Pages | L824-36 |
| PubMed ID | 26944089 | Mgi Jnum | J:234352 |
| Mgi Id | MGI:5789833 | Doi | 10.1152/ajplung.00350.2015 |
| Citation | Sun KH, et al. (2016) alpha-Smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent TGFbeta activation or collagen production across multiple models of organ fibrosis. Am J Physiol Lung Cell Mol Physiol 310(9):L824-36 |
| abstractText | 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 TGFbeta 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, alpha-smooth muscle actin (alphaSMA) is often used to identify pathologic fibroblasts, and some authors have equated alphaSMA(+) cells with contractile myofibroblasts and proposed that these cells are the major source of ECM. Here, we investigated how well alphaSMA expression describes fibroblast subsets responsible for TGFbeta activation and collagen production in three commonly used models of organ fibrosis that we previously reported could be inhibited by loss of alphav integrins on all fibroblasts (using PDGFRbeta-Cre). Interestingly, alphaSMA-directed deletion of alphav integrins protected mice from CCl4-induced hepatic fibrosis, but not bleomycin-induced pulmonary or unilateral ureteral obstruction-induced renal fibrosis. Using Col-EGFP/alphaSMA-RFP dual reporter mice, we found that only a minority of collagen-producing cells coexpress alphaSMA in the fibrotic lung and kidney. Notably, Col-EGFP(+)alphaSMA-RFP(-) cells isolated from the fibrotic lung and kidney were equally capable of activating TGFbeta as were Col-EGFP(+)alphaSMA-RFP(+) cells from the same organ, and this TGFbeta activation was blocked by a TGFbeta-blocking antibody and an inhibitor of nonmuscle myosin, respectively. Taken together, our results suggest that alphaSMA is an inconsistent marker of contractile and collagen-producing fibroblasts in murine experimental models of organ fibrosis. |
