| First Author | Zhou Y | Year | 2014 |
| Journal | J Cell Sci | Volume | 127 |
| Issue | Pt 20 | Pages | 4494-506 |
| PubMed ID | 25107369 | Mgi Jnum | J:216306 |
| Mgi Id | MGI:5608625 | Doi | 10.1242/jcs.155523 |
| Citation | Zhou Y, et al. (2014) Secreted fibroblast-derived miR-34a induces tubular cell apoptosis in fibrotic kidney. J Cell Sci 127(Pt 20):4494-506 |
| abstractText | Tubular epithelial cell apoptosis contributes to tubulointerstitial fibrosis but its regulation remains unclear. Here, in fibrotic kidney induced by unilateral ureteral obstruction (UUO), we demonstrate that miR-34a is markedly upregulated in tubulointerstitial spaces and microvesicles isolated from obstructed kidney. However, miR-34a is not de novo synthesized by proximal tubular epithelial cells but by fibroblasts after incubation with TGF-beta1. miR-34a is markedly upregulated in microvesicles isolated from the cell culture medium of TGF-beta1-treated fibroblasts. These microvesicles act as a vector for delivery of upregulated miR-34a from fibroblasts to tubular cells. The fibroblast-derived miR-34a-containing microvesicles induce the apoptosis of tubular cells. The exogenous miR-34a regulates tubular apoptosis by modulating the expression of the anti-apoptotic protein Bcl-2. Moreover, injection of exogenous miR-34a-containing microvesicles enhances tubular cell apoptosis in mice. This study suggests that secreted fibroblast miR-34a transported by microvesicles induces tubular cell apoptosis in obstructed kidney. This study reveals a new mechanism whereby microvesicle-mediated communication of miRNA between fibroblasts and tubular cells is involved in regulating tubular cell apoptosis, which might provide new therapeutic targets for renal tubulointerstitial fibrosis. |
