Effects of hydrogen sulfide on high glucose-induced glomerular podocyte injury in mice.
The aim of this study was to assess the effects of hydrogen sulfide on high glucose-induced mouse podocyte (MPC) injury and the underlying mechanisms. Mouse podocytes were randomly divided into 4 groups, including high glucose (HG), normal glucose (NG), normal glucose + DL-propargylglycine (PPG), and high glucose + NaHS (HG + NaHS) groups for treatment. Then, ZO-2, nephrin, β-catenin, and cystathionine γ-lyase (CSE) protein expression levels were determined by western blot. We found that high glucose significantly reduced nephrin, ZO-2, and CSE expression levels (P<0.05), and overtly elevated β-catenin amounts (P<0.05), in a time-dependent manner. Likewise, PPG at different concentrations in normal glucose resulted in significantly lower CSE, ZO-2, and nephrin levels (P<0.05), and increased β-catenin amounts (P<0.05). Interestingly, significantly increased ZO-2 and nephrin levels, and overtly reduced β-catenin amounts were observed in the HG + NaHS group compared with HG treated cells (P<0.01). Compared with NG treated cells, decreased ZO-2 and nephrin levels and higher β-catenin amounts were obtained in the HG + NaHS group. In conclusion,CSE downregulation contributes to hyperglycemia induced podocyte injury, which is alleviated by exogenous H2S possibly through ZO-2 upregulation and the subsequent suppression of Wnt/β-catenin pathway.
Department of Nephrology, The Second Hospital of Shandong University Jinan, Shandong, China ; Yantai Affiliated Hospital of Binzhou Medical University Binzhou, Shandong, China.
Ye
Y
Liu
Department of Nephrology, The Second Hospital of Shandong University Jinan, Shandong, China.
Huichen
H
Zhao
Department of Endocrinology, Qingdao Municipal Hospital Qingdao, Shandong, China.
Ye
Y
Qiang
Department of Endocrinology, Traditional Chinese Medicine Hospital of Zhangqiu Zhangqiu, Shandong, China.
Guanfang
G
Qian
Department of Cardiology, Shandong Electric Power Central Hospital Jinan, China.
Shengxia
S
Lu
Institute of Cell Biology, Shandong University Jinan, China.
Jicui
J
Chen
Institute of Cell Biology, Shandong University Jinan, China.
Xiangdong
X
Wang
Provincial Hospital affiliated to Shandong University Jinan, China.
Qingbo
Q
Guan
Department of Endocrinology, Qingdao Municipal Hospital Qingdao, Shandong, China.
Yuantao
Y
Liu
Department of Nephrology, The Second Hospital of Shandong University Jinan, Shandong, China.
Yuqin
Y
Fu
D000480:Alkynes / Q000494:pharmacology; D002478:Cells, Cultured; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D019610:Cytoprotection; D005947:Glucose / Q000633:toxicity*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology*; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D060449:Wnt Signaling Pathway / Q000187:drug effects; D062827:Zonula Occludens-2 Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D000480:Alkynes; C495267:CTNNB1 protein, mouse; D008565:Membrane Proteins; D020011:Protective Agents; D013440:Sulfides; C569047:Tjp2 protein, mouse; D062827:Zonula Occludens-2 Protein; D051176:beta Catenin; C113267:nephrin; C009055:propargylglycine; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D005947:Glucose; D005998:Glycine; D006862:Hydrogen Sulfide
CSE; Diabetic nephropathy; ZO-2; hydrogen sulfide; podocytes; β-catenin