Follistatin-Like Protein 1 Alleviates Renal Ischemia-Reperfusion Injury by Regulating MicroRNA-21

Abstract

A mouse renal ischemia-reperfusion injury (RIRI) model was used to investigate how follistatin-Like Protein 1 (FSTL1) provides renal protection post-RIRI by targeting inflammation, apoptosis, and microRNA (miRNA). RIRI was induced in 8-week-old male C57BL/6 mice, followed by FSTL1 recombinant protein treatment. Inflammation and apoptosis in kidney tissues were assessed using ELISA and flow cytometry. A cellular RIRI model was created using hypoxia/reoxygenation (H/R) in HK-2 cells to validate FSTL1’s effects. miRNA-mediated mechanisms were explored using cell transfection and dual-luciferase assays. RIRI mice exhibited elevated inflammation and apoptosis, while FSTL1 treatment mitigated these effects. Similarly, FSTL1 attenuated H/R-induced HK-2 cell damage. miR-21 expression decreased in H/R-treated HK-2 cells, which FSTL1 reversed. miR-21 mimic reduced H/R-induced HK-2 cell damage, while its inhibition decreased FSTL1’s protection. Notably, miR-21 targeted caspase-7 and suppressed its activity. FSTL1 alleviated mouse RIRI by upregulating miR-21, thereby reducing inflammation and apoptosis in kidney tissues post-RIRI. This study highlights FSTL1’s therapeutic potential through the miR-21-mediated regulation of inflammation and apoptosis in RIRI.