| First Author | Kim JI | Year | 2013 |
| Journal | Biochim Biophys Acta | Volume | 1832 |
| Issue | 10 | Pages | 1520-7 |
| PubMed ID | 23639629 | Mgi Jnum | J:202385 |
| Mgi Id | MGI:5518970 | Doi | 10.1016/j.bbadis.2013.04.021 |
| Citation | Kim JI, et al. (2013) Defect in Runx2 gene accelerates ureteral obstruction-induced kidney fibrosis via increased TGF-beta signaling pathway. Biochim Biophys Acta 1832(10):1520-7 |
| abstractText | Runt-related transcription factor 2 (Runx2) plays an important role in bone formation and de novo synthesis of proteins, including type 1 collagen. Runx2 has a potent effect on signaling of transforming growth factor (TGF)-beta and vice versa, implicating its significant role in fibrosis. Chronic renal failure comprises fibrosis, characterized as an increase in TGF-beta signaling, and expression of alpha-smooth muscle actin (alpha-SMA), and extracellular matrix proteins. Here, we evaluated the role of Runx2 in ureteral obstruction (UO)-induced kidney fibrosis using mice whose Runx2 gene expression is genetically down-regulated. UO caused tubular atrophy and dilation, expansion of interstitium, and increased expression of collagens and alpha-SMA with a concomitant decrease in expression of Runx2. Deficiency of Runx2 gene (Runx2(+/-) mice) showed higher expression of collagens and alpha-SMA in the kidney following UO compared to wild type (Runx2(+/+)) mice. UO-induced activation of TGF-beta signaling was higher in the Runx2(+/-) kidney than Runx2(+/+) kidney, suggesting an inhibitory effect of Runx2 on TGF-beta signaling in kidney fibrosis. Besides, overexpression of the Runx2 gene using an adenoviral vector in kidney tubule cells resulted in attenuated TGF-beta-induced Smad3 phosphorylation and expressions of alpha-SMA and collagen I. Furthermore, Runx2 gene deficient mouse embryonic fibroblasts induced greater activation of Smad3 and expression of alpha-SMA in response to TGF-beta. Collectively, Runx2 plays a protective role in UO-induced kidney fibrosis by inhibition of TGF-beta signaling, suggesting Runx2 as a novel target for protection against fibrosis-related diseases such as chronic renal failure. |
