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TRF-Val-TAC-004 protects against renal ischemia-reperfusion injury via attenuating Apaf1-mediated apoptosis

ABSTRACT: tRNA-derived fragments (tRFs) play critical roles in cellular process, and we have previously reported that tRFs is involved in ischemia reperfusion injury induced acute kidney injury (IRI-AKI). However, the precise involvement of tRFs in IRI-AKI remains obscure. This study aims to elucidate the impact of tRF-Val-TAC-004 (tRF-Val) on IRI-AKI and to uncover the underlying mechanisms. Our observations reveal a significant downregulation of tRF-Val in the kidneys of ischemic mice. Overexpression of tRF-Val mitigated renal dysfunction, morphological damage, and tubular cells apoptosis in IRI-AKI mice, while its inhibition exacerbated these effects. Similar outcomes were replicated in CoCl2-treated BUMPT cells upon transfection with tRF-Val mimic or inhibitor. Mechanistically, dual-luciferase reporter assays and AGO-RIP qPCR analyses demonstrated that tRF-Val suppresses Apaf1 expression by targeting the 3’-UTR of Apaf1 mRNA through AGO-dependent sequence complementarity. Furthermore, the protective efficacy of tRF-Val was notably weakened when Apaf1-overexpressing plasmids were transfected into CoCl2-treated BUMPT cells. In summary, these novel findings unveil the protective role of tRF-Val against IRI-AKI through inhibition of Apaf1-mediated apoptosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE282997 | GEO | 2024/12/18

REPOSITORIES: GEO

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