Treatise:Mechanism and Practice

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

  • Lianpeng YANG ,
  • Ning DING ,
  • Ziqing WANG ,
  • Yining TIAN ,
  • Yichen WANG ,
  • Yideng JIANG ,
  • Guanjun LU
Expand
  • 1.The First Clinical Medical College of Ningxia Medical University,Yinchuan 750004,Ningxia,China
    2.NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan 750004,Ningxia,China
    3.The Second Surgical Department,Qinghai Provincial Hospital of Traditional Chinese Medicine,Xining 810000,Qinghai,China
    4.Department of Urology,Ningxia Medical University General Hospital,Yinchuan 750004,Ningxia,China

Received date: 2026-05-25

  Online published: 2026-08-05

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.

Cite this article

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 . DOI: 10.3969/j.issn.1006-5725.2026.14.011

References

[1] PRICE I N, WOOD A F. Chronic kidney disease and renal replacement therapy: An overview for the advanced clinical practitioner[J]. Br J Nurs, 2022, 31(3): 124-134. doi:10.12968/bjon.2022.31.3.124 .
[2] BRADACS I A, BáBA L I, LORENZOVICI L, et al. Epidemiology and hospitalization costs of chronic kidney disease in Romania [J]. Health Econ Rev, 2025, 15(1): 38. doi:10.1186/s13561-025-00614-x .
[3] HAYASHI K. Targeting DNA methylation in podocytes to overcome chronic kidney disease[J]. Keio J Med, 2023, 72(3): 67-76. doi:10.2302/kjm.2022-0017-IR .
[4] ZHANG J, ZHANG Y, ZHANG Q, et al. High glucose promotes podocyte movement: From the perspective of single cell motility assay[J]. Cell Biol Int, 2023, 47(4): 823-830. doi:10.1002/cbin.11996 .
[5] WU D F, YIN R X, DENG J L. Homocysteine, hyperhomocysteinemia, and H-type hypertension[J]. Eur J Prev Cardiol, 2024, 31(9): 1092-1103. doi:10.1093/eurjpc/zwae022 .
[6] 卢冠军, 汪乐新, 赵静, 等. 瞬时感受电位通道6在同型半胱氨酸诱导的小鼠肾脏足细胞自噬中的作用[J]. 解放军医学杂志, 2024, 49(12): 1400-1407. doi:10.11855/j.issn.0577-7402. 0248.2024.0721 .
[7] 李小琴, 汪乐新, 马小军, 等. 高同型半胱氨酸经TRPC6/NF-κB诱导肾小球足细胞铁死亡的机制 [J]. 实用医学杂志, 2024, 40(02): 174-181.doi:10.3969/j.issn.1006-5725.2024. 02.009 .
[8] 王子清, 丁宁, 杨连鹏, 等. circ_0001126在同型半胱氨酸导致的MPC-5细胞铁死亡中的作用[J]. 实用医学杂志, 2026, 42(2): 201-211. doi:10.3969/j.issn.1006-5725.2026.02.005 .
[9] XIE L, MA S, DING N, et al. Homocysteine induces podocyte apoptosis by regulating miR-1929-5p expression throughc-Myc, DNMT1 and EZH2[J]. Mol Oncol, 2021, 15(11): 3203-3221. doi:10.1002/1878-0261.13032 .
[10] ARNOULD S, BENASSAYAG C, MERLE T, et al. Epithelial apoptosis: A back-and-forth mechanical interplay between the dying cell and its surroundings[J]. Semin Cell Dev Biol, 2025, 168: 1-12. doi:10.1016/j.semcdb.2025.02.001 .
[11] DUDZIK J, CZECHOWICZ P, WI?CH-WALóW A, et al. PiRNAs, piRNA-like, and PIWI proteins in somatic cells: From genetic regulation to disease mechanisms[J]. Wires RNA, 2025, 16(2): e70012. doi:10.1002/wrna.70012 .
[12] DENG X, LIAO T, XIE J, et al. The burgeoning importance of PIWI-interacting RNAs in cancer progression[J]. Sci China Life Sci, 2024, 67(4): 653-662. doi:10.1007/s11427-023-2491-7 .
[13] JIANG M, HONG X, GAO Y, et al. PiRNA associates with immune diseases[J]. Cell Commun Signal, 2024, 22(1): 347. doi:10.1186/s12964-024-01724-5 .
[14] VAN ZONNEVELD A J, ZHAO Q, ROTMANS J I, et al. Circulating non-coding RNAs in chronic kidney disease and its complications[J]. Nat Rev Nephrol, 2023, 19(9): 573-586. doi:10.1038/s41581-023-00725-w .
[15] CHEN S, BEN S, XIN J, et al. The biogenesis and biological function of PIWI-interacting RNA in cancer[J]. J Hematol Oncol, 2021, 14(1): 93. doi:10.1186/s13045-021-01104-3 .
[16] 武霄雷, 韩瑜, 李佳蕾,等. piRNA-5938可调控心肌细胞凋亡和线粒体分裂 [J]. 中国组织工程研究, 2023, 27(11): 1750-7.doi:10.12307/2023.125 .
[17] WANG X, RAMAT A, SIMONELIG M, et al. Emerging roles and functional mechanisms of PIWI-interacting RNAs[J]. Nat Rev Mol Cell Biol, 2023, 24(2): 123-141. doi:10.1038/s41580-022-00528-0 .
[18] 张正皓, 马芳, 张晴, 等. LncRNA SNHG1在同型半胱氨酸致足细胞焦亡中的作用[J]. 实用医学杂志, 2024, 40(4): 476-482. doi:10.3969/j.issn.1006-5725.2024.04.007 .
[19] KUMARI S, SINGH P P, KUMAR D, et al. Intact Parathyroid Hormone (iPTH) Assay: An Early Approach for Bone Health Assessment in Chronic Renal Failure [J]. Cureus, 2024, 16(10): e72510.doi:10.7759/cureus.72510 .
[20] JAIMES E A, ZHOU M S, SIDDIQUI M, et al. Nicotine, smoking, podocytes, and diabetic nephropathy[J]. Am J Physiol Renal Physiol, 2021, 320(3): F442-F453. doi:10.1152/ajprenal.00194.2020 .
[21] NISHIMURA Y. Podocytes in health and disease: From development to regeneration[J]. Hum Cell, 2025, 38(6): 169. doi:10.1007/s13577-025-01296-7 .
[22] PARK E J, JE J, DUSABIMANA T, et al. The uremic toxin homocysteine exacerbates the brain inflammation induced by renal ischemia-reperfusion in mice[J]. Biomedicines, 2022, 10(12): 3048. doi:10.3390/biomedicines10123048 .
[23] CHEN S M, TANG X Q. Homocysteinylation and sulfhydration in diseases[J]. Curr Neuropharmacol, 2022, 20(9): 1726-1735. doi:10.2174/1570159x20666211223125448 .
[24] 常辈辈, 全会标. 血清同型半胱氨酸与糖尿病慢性并发症关系的研究进展 [J]. 海南医学, 2022, 33(18): 2418-21.doi:10.3969/j.issn.1003-6350.2022.18.029 .
[25] 揭育祯, 丁宁, 谢琳, 等. 同型半胱氨酸上调miR-488-3p表达诱导MPC-5小鼠肾小球足细胞凋亡 [J]. 细胞与分子免疫学杂志, 2022, 38(9): 801-6.doi:10.13423/j.cnki.cjcmi.009470 .
[26] DING N, XIE L, MA F, et al. miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia [J]. Acta Biochim Biophys Sin (Shanghai), 2022, 54(1): 126-136.doi:10.3724/abbs.2021005 .
[27] GEBERT D, NEUBERT L K, LLOYD C, et al. Large Drosophila germline piRNA clusters are evolutionarily labile and dispensable for transposon regulation [J]. Mol Cell, 2021, 81(19): 3965-3978.e5.doi:10.1016/j.molcel.2021.07.011 .
[28] 舒玉林, 陈小红, 李昌平. piRNA在肝脏相关疾病中的研究进展 [J]. 现代临床医学, 2024, 50(2): 131-134.doi:10.11851/j.issn.1673-1557.2024.02.014 .
[29] SARITAS G, MAIN A M, WINGE S B, et al. PIWI-interacting RNAs and human testicular function [J]. WIREs Mech Dis, 2022, 14(6): e1572.doi:10.1002/wsbm.1572 .
[30] WANG K, WANG T, GAO X Q, et al. Emerging functions of piwi-interacting RNAs in diseases [J]. J Cell Mol Med, 2021, 25(11): 4893-4901.doi:10.1111/jcmm.16466 .
[31] RAY S K, MUKHERJEE S. Piwi-interacting RNAs (piRNAs) and Colorectal Carcinoma: Emerging Non-invasive diagnostic Biomarkers with Potential Therapeutic Target Based Clinical Implications [J]. Curr Mol Med, 2023, 23(4): 300-311.doi:10.2174/1566524022666220124102616 .
[32] LI B, WANG K, CHENG W, et al. Recent advances of PIWI-interacting RNA in cardiovascular diseases [J]. Clin Transl Med, 2024, 14(8): e1770.doi:10.1002/ctm2.1770 .
[33] ZHOU J, XIE H, LIU J, et al. PIWI-interacting RNAs: Critical roles and therapeutic targets in cancer [J]. Cancer Lett, 2023, 562: 216189.doi:10.1016/j.canlet.2023.216189 .
[34] RADAN M, ATEFIPOUR N, ABEDIZADEH P, et al. Tannic acid inhibits diquat induced human renal HK-2 cells apoptosis through BAX/Bcl2/caspase/cleaved caspase-3 signaling pathway [J]. Biomed Eng Online, 2025, 24(1): 148.doi:10.1186/s12938-025-01484-4 .
[35] TAN W, LI Y, MA L, et al. Exosomes of endothelial progenitor cells repair injured vascular endothelial cells through the Bcl2/Bax/Caspase-3 pathway [J]. Sci Rep, 2024, 14(1): 4465.doi:10.1038/s41598-024-55100-x .
Outlines

/