| First Author | Guan S | Year | 2017 |
| Journal | Exp Cell Res | Volume | 359 |
| Issue | 1 | Pages | 226-234 |
| PubMed ID | 28736081 | Mgi Jnum | J:262102 |
| Mgi Id | MGI:6152331 | Doi | 10.1016/j.yexcr.2017.07.025 |
| Citation | Guan S, et al. (2017) Frizzled-7 mediates TGF-beta-induced pulmonary fibrosis by transmitting non-canonical Wnt signaling. Exp Cell Res 359(1):226-234 |
| abstractText | Pulmonary fibrosis is a progressive and often fatal lung disease characterized by fibroblast proliferation and excessive deposition of extracellular matrix. Both TGF-beta and Wnt signaling have been implicated in the regulation of organ fibrosis. However little is known about whether TGF-beta-induced gene expression changes in Wnt signaling pathway could predict disease progression. In the study, we investigated the interaction between TGF-beta and Wnt signaling in mediating pulmonary fibrosis by big data analysis, in vitro and in vivo experimental studies and clinical data analysis. We found that TGF-beta1 treatment induces a marked upregulation of Frizzled-7 (FZD7) in human lung fibroblasts. FZD7 expression is also increased in animal models of TGF-beta1-induced pulmonary fibrosis. TGF-beta1 upregulated FZD7 expression in a Smad3-dependent manner. Functionally, knockdown of FZD7 inhibits TGF-beta1-induced expression of alpha-smooth muscle actin (alpha-SMA), collagen I (Col I), fibronectin and connective tissue growth factor (CTGF). FZD7 inhibition further attenuates TGF-beta1-induced pulmonary fibrosis in vivo. Finally our data demonstrated that FZD7 transmits non-canonical Wnt signaling by interacting Wnt5A in the regulation of ECM expression. CONCLUSION: These results suggest that FZD7-targeted therapeutic strategies may be applicable for treating an array of fibrotic diseases. |
