Chronic kidney disease (CKD) is thus deemed to a global health problem. Renal
fibrosis, characterized by accumulation of extracellular matrix (ECM) components in the kidney, is considered a common pathway leading to CKD. Regulator of calcineurin1 (RCAN1), identified as a competitive endogenous inhibitor of the
phosphatase calcineurin, participates in ECM deposition in various organs. However, the role of RCAN1 in renal
fibrosis remains unclear. Here, unilateral
ureteral obstruction (UUO), a well-known model to induce renal
fibrosis in vivo, was performed on mice for a week. To overexpress RCAN1.4 in vivo, recombinant adeno-associated virus 9-packed RCAN1.4 over-expression plasm was employed in mice kidney. Lentivirus-packed RCAN1.4 over-expression plasm was employed to transfer into HK-2 and NRK-49F cells in vitro. The results indicated that RCAN1.4 expression was impaired both in UUO-induced renal
fibrosis in vivo and TGF-β1-induced renal
fibrosis in vitro. However, knocking in of RCAN1.4 suppressed the production of extracellular matrix (ECM) both in vivo and in vitro. Furthermore, in vitro, the apoptosis-related
proteins, including the ratio of Bax/Bcl-2 and cleaved-caspase3, were elevated in cells transfected with RCAN1.4 overexpression plasmid. In addition, we found that RCAN1.4 could rugulated NFAT2 nuclear distribution by inhibiting
calcineurin pathway. So overexpression of RCAN1.4 could reverse renal
fibrosis, attenuate ECM related
protein accumulation, promote apoptosis of myofibroblast via inhibiting
Calcineurin/NFAT2 signaling pathway. Taken together, our study demonstrated that targeting RCAN1.4 may be therapeutic efficacy in renal
fibrosis.