| First Author | Zhou Z | Year | 2020 |
| Journal | J Mol Med (Berl) | Volume | 98 |
| Issue | 4 | Pages | 527-540 |
| PubMed ID | 32036390 | Mgi Jnum | J:357999 |
| Mgi Id | MGI:6881552 | Doi | 10.1007/s00109-020-01879-x |
| Citation | Zhou Z, et al. (2020) RIG-I aggravates interstitial fibrosis via c-Myc-mediated fibroblast activation in UUO mice. J Mol Med (Berl) 98(4):527-540 |
| abstractText | Progressive tubulointerstitial fibrosis is the common final outcome for all kidney diseases evolving into chronic kidney disease (CKD), whereas molecular mechanisms driving fibrogenesis remain elusive. Retinoic acid-inducible gene-I (RIG-I), an intracellular pattern recognition receptor, is originally identified participating in immune response by recognizing virus RNA. Here, we revealed for the first time that RIG-I was induced in unilateral ureteral obstruction (UUO) and folic acid (FA) renal fibrosis models and moderate-degree renal fibrosis patients. Besides, we found RIG-I was mainly located in renal tubular epithelial cells and promoted the production and release of inflammatory cytokines, such as interleukin (IL)-1beta and IL-6 through activation of NF-kappaB. Inflammatory cytokines released by tubular epithelial cells activated c-Myc-mediated TGF-beta/Smad signaling in fibroblasts, which in turn aggravated interstitial fibrosis by promoting fibroblast activation and production of extracellular matrix components (ECM). Deficiency of RIG-I attenuated renal fibrosis by the regulation of inflammatory responses, c-Myc expression, and fibroblast activation. Besides, gene silencing of RIG-I reduced inflammatory cytokines in cultured tubular epithelial cells treated with Angiotensin II. Knockdown of c-Myc or c-Myc inhibitor blocked IL-1beta-induced fibroblast activation. Collectively, our study demonstrates that RIG-I plays a significant role in the progress of renal fibrosis via regulating c-Myc-mediated fibroblast activation. KEY MESSAGES: * RIG-I was constantly elevated in kidneys from renal fibrotic mice. * RIG-I facilitated inflammatory cytokine production in tubular epithelial cells. * RIG-I aggravated renal fibrosis via c-Myc-mediated TGF-beta/Smad activation. |
