Basic Research

Effect of LncRNA SNHG1 on homocysteine⁃induced podocytespyrophosis

  • Zhenghao ZHANG ,
  • Fang MA ,
  • Qing ZHANG ,
  • Tongtong XIA ,
  • Honglin LIU ,
  • Zhigang BAI ,
  • Guanjun LU ,
  • Jingwen ZHANG ,
  • Hongjian PENG ,
  • Yideng JIANG ,
  • Shengchao. MA
Expand
  • *. School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China
    NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Yinchuan 750004,China

Received date: 2023-06-27

  Online published: 2024-03-08

Abstract

Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte. Methods Cbs +/- mice were randomly divided into two groups: a normal diet group (ND) and a high methionine diet group (HMD). Western blotting was used to detect the protein expression levels of Caspase-1, Cleaved Caspase-1, and NLRP3. Mouse renal glomerular podocytes were cultured in vitro, and then assigned into a control group (Control, 0 μmol/L Hcy) and a homocysteine intervention group(Hcy, 80 μmol/L Hcy). Western blotting was used to detect the protein expression levels of Caspase-1, Cleaved Caspase-1, and NLRP3. Mouse renal glomerular podocyion group (OE-NC + Hcy) and the lncSNHG1 overexpression + homocysteine intervention group (OE-SNHG1 + Hcy) were also established.After 48 hours of intervention, Real-time fluorescence quantitative PCR was used to detect the expression of lncSNHG1 in podocytes after Hcy intervention. Western blot was used to detect the expressions of Caspase-1,Cleaved Caspase-3 and NLRP3. Immunofluorescence was used to detect the expression levels of GSDMD and GSDMD-N. ELISA was used to detect the contents of IL-1β and IL-18. Results (1)In the animal experiments, the expression levels of pyroptosis-related proteins Caspase-1, Cleaved Caspase-1,NLRP3, GSDMD, and GSDMD-N were all increased in the HMD group compared with the ND group. (2)In the cellular experiments, the expression levels of Caspase-1,Cleaved Caspase-1,NLRP3, GSDMD, and GSDMD-N were all increased in the Hcy group compared with the Control group, and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased as well. (3) In the cellular experiments, the expression of lncSNHG1 was increased in the Hcy group compared with the control group. After transduction with lncSNHG1 lentivirus, the expression of lncSNHG1 was increased in the OE-SNHG1 group,compared with the control group and the OE-NC group. (4)In the cellular experiments, the expressions of pyroptosis-related proteins Caspase-1,Cleaved Caspase-1, NLRP3, GSDMD,and GSDMD-N were increased compared with the OE-NC+Hcy group, and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased in the OE-SNHG1+Hcy group. Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis.

Cite this article

Zhenghao ZHANG , Fang MA , Qing ZHANG , Tongtong XIA , Honglin LIU , Zhigang BAI , Guanjun LU , Jingwen ZHANG , Hongjian PENG , Yideng JIANG , Shengchao. MA . Effect of LncRNA SNHG1 on homocysteine⁃induced podocytespyrophosis[J]. The Journal of Practical Medicine, 2024 , 40(4) : 476 -482 . DOI: 10.3969/j.issn.1006-5725.2024.04.007

References

1 MUTAIRI F AL . Hyperhomocysteinemia: Clinical Insights[J]. J Cent Nerv Syst Dis, 2020, 12: 1179573520962230. doi:10.1177/1179573520962230
2 MIZUNO T , HOSHINO T , ISHIZUKA K , et al . Hyperhomocysteinemia Increases Vascular Risk in Stroke Patients with Chronic Kidney Disease[J]. J Atheroscler Thromb, 2022: 11-26. doi:10.5551/jat.63849
3 赵若蓓, 罗宇珍, 潘玲, 等 . 足突融合与IgA肾病临床病理特征及肾功能的关系[J]. 实用医学杂志, 2021,37(10): 1268-1271. doi:10.3969/j.issn.1006-5725.2021.10.007
4 ZHANG M , YUAN J , DONG R , et al . Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis[J]. Open Life Sci, 2021, 16: 537-543. doi:10.1515/biol-2021-0054
5 CUI Y , ZHANG F , ZHU C , et al . Upregulated lncRNA SNHG1 contributes to progression of non-small cell lung cancer through inhibition of miR-101-3p and activation of Wnt/β-catenin signaling pathway[J]. Oncotarget, 2017, 8(11): 17785-17794. doi:10.18632/oncotarget.14854
6 THIN K Z , TU J C , RAVEENDRAN S . Long non-coding SNHG1 in cancer[J]. Clin Chim Acta, 2019, 494:38-47. doi:10.1016/j.cca.2019.03.002
7 NAGATA M . Podocyte injury and its consequences[J]. Kidney international, 2016, 89(6): 1221-1230. doi:10.1016/j.kint.2016.01.012
8 张鸿,梁顺,杜玥,等 . 核因子κB受体活化因子通过TRPC6-NFATc1信号通路介导足细胞损伤[J]. 实用医学杂志, 2019,35(1):25-29,34. doi:10.3969/j.issn.1006-5725.2019.01.006
9 CONLEY S M , ABAIS-BATTAD J M , YUAN X , et al . Contribution of guanine nucleotide exchange factor Vav2 to NLRP3 inflammasome activation in mouse podocytes during hyperhomocysteinemia[J]. Free Radic Biol Med, 2017, 106:236-244. doi:10.1016/j.freeradbiomed.2017.02.027
10 KAYAGAKI N , STOWE I B , LEE B L , et al . Caspase-llcleavesgasdermin D for non-canonical inflammasomesignalling[J]. Nature, 2015, 526(7575): 666-671. doi:10.1038/nature15541
11 AN X , ZHANG Y , CAO Y , et al . Punicalagin protects diabetic nephropathy by inhibiting pyroptosis based on TXNIP/NLRP3 pathway[J]. Nutrients, 2020, 12(5): 1516. doi:10.3390/nu12051516
12 LIN J , CHENG A , CHENG K , et al . New insights into the mechanisms of pyroptosis and implications for diabetic kidney disease[J]. Int J Mol Sci, 2020, 21(19): 7057. doi:10.3390/ijms21197057
13 李冰,熊正方,郭亚民 . 长链非编码胰RNA ROR通过notch1蛋白调控腺癌细胞的增殖凋亡[J]. 实用医学杂志, 2017, 33(12): 1922-1927.
14 ZHANG H , ZHOU D , YING M , et al . Expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) exacerbates hepatocellular carcinoma through suppressing miR-195[J]. Med Sci Monit, 2016, 22(12): 4820-4829. doi:10.12659/msm.898574
15 LEI J , FU Y , ZHUANG Y , et al . LncRNA SNHG1 alleviates IL-1β-induced osteoarthritis by inhibiting miR-16-5pmediated p38 MAPK and NF-κB signaling pathways[J]. Biosci Rep, 2019, 39(9): BSR20191523. doi:10.1042/bsr20191523
16 XU J H , RUI Y , HUA X H , et al . lncRNA SNHG1 promotes basal bladder cancer invasion via interaction with PP2A catalytic subunit and induction of autophagy[J]. Mol Ther Nucleic Acids, 2020, 21: 354-366. doi:10.1016/j.omtn.2020.06.010
17 ZHAO S , WANG Y , LUO M , et al . Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) promotes renal cell carcinoma progression and metastasis by negatively regulating miR-137[J]. Med Sci Monit, 2018, 24: 3824-3831. doi:10.12659/msm.910866
Outlines

/