MiR-511-3p upregulates fibrosis-related proteins expression by targeting CAMK2N1 in renal interstitial fibrosis.

Renal interstitial fibrosis (RIF) is a crucial pathophysiological manifestation of chronic kidney disease (CKD). MicroRNAs (miRNAs) are pivotal in post-transcriptional regulation and play significant roles in the pathogenesis of RIF. However, the underlying mechanism of miRNAs in RIF remains unclear. In our study, we screened the differentially expressed miRNAs in RIF models by high-throughput sequencing, and found that miR-511-3p was significantly increased in the RIF group. Therefore, we speculated that miR-511-3p might play a role in RIF. Further experiments including FISH and qRT-PCR were used to detect the expression and localization of miR-511-3p. HE, Masson and IHC staining evaluated morphological changes of RIF. Western Blot detected the protein levels. Targetscan database and luciferase reporter assay predicted and confirmed the binding between miR-511-3p and its target genes. In this study, we initially discovered that miR-511-3p was notably increased in renal patients with RIF, unilateral ureteral obstruction (UUO) mice, and human renal tubular epithelium cells (HK-2) treated with TGF-β1. Additionally, the overexpression of miR-511-3p showed a pro-renal interstitial fibrosis effect, whereas its inhibition suppressed RIF. Mechanistically, calcium/calmodulin-dependent protein kinase II inhibitor 1 (CAMK2N1) was identified as a potential binding target gene for miR-511-3p. Further results showed miR-511-3p bound to the 3'UTR of CAMK2N1 and hindered the expression of CAMK2N1. Furthermore, it has been demonstrated that CAMK2N1 inhibits RIF, and its overexpression reversed the pro-renal interstitial fibrosis effect of miR-511-3p. Our study suggested that miR-511-3p promoted RIF by inhibiting CAMK2N1, which provides a potential novel target for the treatment of CKD.