tRF-Val-TAC-004 protects against renal ischemia-reperfusion injury via attenuating Apaf1-mediated apoptosis
Ni Yin,
Xian Xie,
Dan Li,
Shikun Yang,
Yan Liu,
Yongzhong Tang,
Hao Zhang,
Wei Zhang
Affiliations
Ni Yin
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, Hunan 410013, China
Xian Xie
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, Hunan 410013, China
Dan Li
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, Hunan 410013, China
Shikun Yang
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, Hunan 410013, China
Yan Liu
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, Hunan 410013, China
Yongzhong Tang
Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Hao Zhang
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, Hunan 410013, China; Corresponding author
Wei Zhang
Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, Hunan 410013, China; Corresponding author
Summary: tRNA-derived fragments (tRFs) play critical roles in cellular process, and we have previously reported that tRFs are 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 uncover the underlying mechanisms. Our observations reveal a significant downregulation of tRF-Val in IRI-AKI mice and its overexpression mitigated renal dysfunction, morphological damage, and 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 assay and AGO-RIP qPCR analyses demonstrated that tRF-Val suppresses Apaf1 expression by targeting the 3′-UTR of Apaf1 mRNA. Furthermore, the protective efficacy of tRF-Val was notably weakened by Apaf1-overexpressing plasmids. In summary, these novel findings unveil the protective role of tRF-Val against IRI-AKI through inhibition of Apaf1-mediated apoptosis.
