| First Author | Zhang H | Year | 2023 |
| Journal | Immunology | Volume | 168 |
| Issue | 1 | Pages | 120-134 |
| PubMed ID | 36053796 | Mgi Jnum | J:374842 |
| Mgi Id | MGI:7782638 | Doi | 10.1111/imm.13567 |
| Citation | Zhang H, et al. (2023) IKKalpha aggravates renal fibrogenesis by positively regulating the Wnt/beta-catenin pathway. Immunology 168(1):120-134 |
| abstractText | AKI (acute kidney injury) with maladaptive repair plays exacerbated role in renal fibrosis characterized by tubulointerstitial fibrosis. Previously, we reported that IKKalpha contributed to kidney regeneration and inhibited inflammation. Here, we first identified the role and mechanism of IKKalpha on TGF-beta1-induced fibrosis in human tubular epithelial cells and fibrotic kidneys. IKKalpha was up-regulated in kidney tubular epithelium in unilateral ureteral obstruction (UUO) and unilateral ischemic reperfusion injury (UIRI) mice. Immunohistochemical staining showed that IKKalpha was positively correlated with the extent of kidney fibrosis in tissue biopsies from chronic kidney disease (CKD) patients. Compared with wild-type controls, Ksp-IKKalpha(-/-) mice exhibited inactivated Wnt/beta-catenin pathway, decreased serum creatinine and interstitial fibrosis in the kidney after IRI. In TGF-beta1-stimulated human tubular epithelial cells, IKKalpha overexpression enhanced beta-catenin nuclear translocation. Blocking IKKalpha by siRNA specifically suppressed beta-catenin activation and downstream profibrotic genes such as fibronectin and alpha-smooth muscle actin (alpha-SMA). Taken together, our study demonstrated that IKKalpha aggravated renal fibrogenesis by activating Wnt/beta-catenin signalling pathway, providing a new target for the treatment of kidney fibrosis. |
