| First Author | Chen J | Year | 2014 |
| Journal | Lab Invest | Volume | 94 |
| Issue | 5 | Pages | 545-56 |
| PubMed ID | 24614197 | Mgi Jnum | J:208401 |
| Mgi Id | MGI:5563262 | Doi | 10.1038/labinvest.2014.43 |
| Citation | Chen J, et al. (2014) Smad3 signaling activates bone marrow-derived fibroblasts in renal fibrosis. Lab Invest 94(5):545-56 |
| abstractText | Recent studies have demonstrated that bone marrow-derived fibroblasts contribute significantly to the pathogenesis of renal fibrosis. However, the signaling mechanisms underlying the activation of bone marrow-derived fibroblasts in the kidney are incompletely understood. As TGF-beta1/Smad3 signaling has been shown to have an important role in the pathogenesis of kidney fibrosis, we investigated the role of Smad3 in the activation of bone marrow-derived fibroblasts in the kidney following obstructive injury using Smad3-knockout mice and Smad3-null monocytes. Compared with wild-type mice, Smad3-knockout mice accumulated significantly fewer bone marrow-derived fibroblasts in the kidney after obstructive injury. Furthermore, Smad3-knockout mice exhibited less myofibroblast activation and expressed less alpha-SMA in the obstructed kidney. Consistent with these findings, genetic deletion of Smad3 reduced total collagen deposition and suppressed the expression of extracellular matrix proteins. Moreover, wild-type mice engrafted with Smad3(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts in the kidney with obstructive injury and showed less severe renal fibrosis compared with wild-type mice engrafted with Smad3(+/+) bone marrow cells. In cultured monocytes, TGF-beta1 induced phosphorylation of Smad3 and Smad3 deficiency abolished TGF-beta1-induced expression of alpha-SMA and extracellular matrix proteins. Taken together, our results demonstrate that Smad3 signaling has an essential role in the activation of bone marrow-derived fibroblasts in the kidney during the pathogenesis of renal fibrosis. |
