piRNA-13663072通过调控Bcl-2/Bax-Caspase-3通路抑制同型半胱氨酸诱导的足细胞凋亡

doi:10.3969/j.issn.1006-5725.2026.14.011

Abstract

Abstract:

Objective To investigate whether piR-13663072 inhibits homocysteine （Hcy）-induced apoptosis in mouse podocyte cell line-5 （MPC-5） by regulating the Bcl-2/Bax-Caspase-3 signaling pathway. Methods A hyperhomocysteinemia （HHcy）-induced kidney injury model was established using Cbs^+/- mice， and RNA sequencing （RNA-seq） was employed to screen for differentially expressed piRNAs in kidney tissues. An in vitro podocyte injury model was created by treating MPC-5 cells with Hcy （80 μmol/L）. The expression of piR-13663072 was verified by quantitative real-time PCR （qRT-PCR）， and its species conservation was analyzed. An overexpression cell model was constructed through the transfection of cells with a piR-13663072 mimic. A silenced cell model was constructed via the transfection of cells with a piR-13663072 inhibitor. The expression levels of apoptosis-related proteins （Bax， Caspase-3， and Bcl-2） were detected via Western blot. The number of apoptotic cells was assessed by propidium iodide （PI） staining， and cytoskeletal morphology was observed using phalloidin staining. Results Hcy intervention notably induced apoptosis in MPC-5 cells （as evidenced by the elevated expressions of the pro-apoptotic proteins Bax and Caspase-3， and the reduced expression of the anti-apoptotic protein Bcl-2）， accompanied by cytoskeletal disruption. RNA-seq and qRT-PCR validation demonstrated that piR-13663072 was significantly downregulated in both the kidneys of mice with HHcy-induced injury and Hcy-treated MPC-5 cells. Moreover， this piRNA exhibits moderate conservation among mammals. Following transfection with the piR-13663072 mimic， the expression level of piR-13663072 was significantly elevated. Overexpression of piR-13663072 suppressed the expressions of Bax and Caspase-3， promoted the expression of Bcl-2， effectively decreased the number of Hcy-induced PI-positive cells， and alleviated cytoskeletal damage. Conversely， transfection with the piR-13663072 inhibitor markedly decreased the level of piR-13663072， upregulated the expressions of Bax and Caspase-3， inhibited the expression of Bcl-2， further increased the number of Hcy-induced PI-positive cells， and exacerbated cytoskeletal damage. Conclusions The expression of piR-13663072 is down-regulated in Hcy-induced podocyte injury. Overexpression of piR-13663072 can effectively inhibit podocyte apoptosis and attenuate cytoskeletal damage through the regulation of the Bcl-2/Bax-Caspase-3 signaling pathway， thus exerting a protective effect on podocytes. In contrast， silencing of piR-13663072 aggravates the aforementioned injuries. Therefore， this molecule shows promise as a potential biomarker and therapeutic target for HHcy-induced kidney injury.

Key words: piRNA-13663072, homocysteine, chronic kidney disease, podocytes, apoptosis

CLC Number:

R692.5

Lianpeng YANG,Ning DING,Ziqing WANG,Yining TIAN,Yichen WANG,Yideng JIANG,Guanjun LU. piR-13663072 inhibits homocysteine-induced podocyte apoptosis via regulating the Bcl-2/Bax-Caspase-3 signaling pathway[J]. The Journal of Practical Medicine, 2026, 42(14): 2577-2587.

Figures/Tables 8

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References 35

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名称		序列（5′→3′）
U6	Forward	CTCGCTTCGGCAGCACA
	Reverse	AACGCTTCACGAATTTGCGT
piR-13663072	Forward	ACCTGAGCGAGGACCAGAAAC
	Reverse	CATTCTGCTGGTCCCCATTTAG
piR-49359979	Forward	AGACAGGGGCCTTTTTGCTAC
	Reverse	AATTCGCCGGAGACACTCG
piR-49535880	Forward	GCTACCGTCGTGACTTCGC
	Reverse	CCCCACCGAACTCAAAGAAGG
piR-67686459	Forward	CTCGCTCTGGTACGGATGTG
	Reverse	TCCCATAAATGACCCCTTCATCA
piR-685550	Forward	AGCGCCTTCCCACATGGTCT
	Reverse	ATCCAGTGCAGGGTCCGAGG

piR-13663072 inhibits homocysteine-induced podocyte apoptosis via regulating the Bcl-2/Bax-Caspase-3 signaling pathway

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