| First Author | You YK | Year | 2021 |
| Journal | Int J Biol Sci | Volume | 17 |
| Issue | 14 | Pages | 3911-3922 |
| PubMed ID | 34671208 | Mgi Jnum | J:312478 |
| Mgi Id | MGI:6786444 | Doi | 10.7150/ijbs.62929 |
| Citation | You YK, et al. (2021) Deletion of Smad3 protects against C-reactive protein-induced renal fibrosis and inflammation in obstructive nephropathy. Int J Biol Sci 17(14):3911-3922 |
| abstractText | Introduction and Aims: Elevated plasma levels of C-reactive protein (CRP) are closely associated with progressive renal injury in patients with chronic kidney disease (CKD). Here, we tested a hypothesis that CRP may promote renal fibrosis and inflammation via a TGF-beta/Smad3-dependent mechanism. Methods: Role and mechanisms of TGF-beta/Smad3 in CRP-induced renal fibrosis and inflammation were examined in a mouse model of unilateral ureteral obstruction (UUO) induced in CRP Tg/Smad3 KO mice and in a rat tubular epithelial cell line in which Smad3 gene is stably knocked down (S3KD-NRK52E). Results: We found that mice overexpressing the human CRP gene were largely promoted renal inflammation and fibrosis as evidenced by increasing IL-1beta, TNF-alpha, MCP-1 expression, F4/80(+) macrophages infiltration, and marked accumulation of alpha-smooth muscle actin (alpha-SMA), collagen I and fibronectin in the UUO kidney, which were blunted when Smad3 gene was deleted in CRPtg-Smad3KO. Mechanistically, we found that the protection of renal inflammation and fibrosis in the UUO kidney of CRPtg-Smad3KO mice was associated with the inactivation of CD32-NF-kappaB and TGF-beta/Smad3 signaling. Conclusion: In conclusion, Smad3 deficiency protects against CRP-mediated renal inflammation and fibrosis in the UUO kidney by inactivating CD32-NF-kappaB and TGF-beta/Smad3 signaling. |
