The role and mechanism of BKCa in mesangial cell injury induced by high glucose

ZHANG Xue; GE Pei; GU Li; LI Hua; ZHANG Dan; HUANG Yuanqong; CHEN Meijuan

doi:10.3969/j.issn.2096-3351.2024.02.008

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The role and mechanism of BKCa in mesangial cell injury induced by high glucose

更新时间：2024-04-11

- The role and mechanism of BKCa in mesangial cell injury induced by high glucose
- Journal of Southwest Medical University Vol. 47, Issue 2, Pages: 136-140(2024)
- 作者机构：
  
  1. 西南医科大学药学院,泸州,646000
  2. 西南医科大学附属医院药学部,泸州,646000
  3. 泸州市中医医院肾内科,泸州,646000
- 作者简介：
- 基金信息：
- DOI：10.3969/j.issn.2096-3351.2024.02.008
  CLC：
- Published：2024，
  
  Published Online：20 March 2024，
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ZHANG Xue, GE Pei, GU Li, et al. The role and mechanism of BKCa in mesangial cell injury induced by high glucose. [J]. Journal of Southwest Medical University 47(2):136-140(2024)
DOI：

ZHANG Xue, GE Pei, GU Li, et al. The role and mechanism of BKCa in mesangial cell injury induced by high glucose. [J]. Journal of Southwest Medical University 47(2):136-140(2024) DOI： 10.3969/j.issn.2096-3351.2024.02.008.

摘要

目的探讨大电导钙激活钾通道（large conductance calcium-activated potassium channel ，BKCa）在糖尿病肾病中的作用及其机制。方法①用激动剂NS11021 和抑制剂Tet 及BKCa-siRNA 干预后观察糖尿病肾病（diabetic nephropathy，DN）细胞模型的细胞增殖率、上清液中Ⅳ型胶原蛋白（collagen Ⅳ，ColⅣ）及纤连蛋白（fibronectin ，FN）的表达变化，揭示BKCa 的作用；②用激动剂NS11021 和抑制剂Tet 及BKCa-siRNA 干预后观察DN 细胞模型TGF-β1、Smad2/3 的含量变化；用激动剂TGF-β1、抑制剂SB431542 干预TGF-β1/ Smad2/3 信号通路后，观察BKCa作用的变化，揭示BKCa作用与该信号通路相关性。结果①与高糖组比较，药理学激动BKCa使模型细胞BKCaβ亚基蛋白表达增加、细胞增殖率增高，差异均具有统计学意义（P < 0.05）；与高糖组比较，药理学和基因抑制BKCa，使其α、β亚基蛋白表达减少，从而出现模型细胞增殖率下降、ColⅣ和FN 分泌明显减少（P < 0.01）。②与高糖组比较，药理学激动BKCa引起Smad2/3 含量增高，药理学和基因抑制BKCa，引起TGF-β1、Smad2/3 含量明显降低，差异均具有统计学意义（P < 0.05）；与NS11021 组比较，用SB431542 阻断TGF-β1/ Smad2/3 信号通路后，细胞增殖率明显降低，ColⅣ和FN 分泌减少，差异均具有统计学意义（P < 0.05）。结论高糖诱导的DN 细胞模型存在BKCa高表达，抑制BKCa后细胞增殖率、ColⅣ和FN 的分泌明显降低，从而改善DN 病变，此作用与TGF-β1/Smad2/3 信号通路相关。

Abstract

Objective To explore the role and mechanism of BKCa（large conductance calcium-activated potassium channel， BKCa）in DN（diabetic nephropathy，DN）. Methods ①After the intervention of agonist NS11021 and inhibitor Tet and BKCa -siRNA，the changes of cell proliferation rate，collagen Ⅳ（ColⅣ）and fibronectin（FN）in the DN cell model were observed to reveal the role of BKCa;②After the intervention of agonist NS11021 and inhibitor Tet and BKCa -siRNA on BKCa，the changes of TGF-β1（Transforming growth factor beta 1）and Smad2/3 were observed in DN cell model ；After the intervention of agonist TGF-β1 and inhibitor SB431542 on TGF-β1/ Smad2/3 signaling pathway ，we observed the change of effects of BKCa on model cells，in order to reveal the correlation between BKCa action and this signaling pathway. Results ①Compared with high glucose group，pharmacologically excited BKCa increased the proliferation rate of model cells，and the expression of BKCa β subunit protein was enhanced，the differences were statistically significant（ P < 0.05）；compared with high glucose group，pharmacological and genetic inhibition of BKCa decreased the expression of α and β subunit protein，the proliferation rate of model cells decreased，and the secretion of ColⅣ and FN decreased significantly（P < 0.01）. ②Compared with the high glucose group，the content of Smad2/3 was increased due to the pharmacological excitation of BKCa，the content of TGF-β1 and Smad2/3 was significantly decreased due to the pharmacological and gene inhibition of BKCa（ the differences were statistically significant（P < 0.05）；compared with NS11021 group，after blocking TGF-β1/ Smad2/3 signaling pathway with SB431542， the cell proliferation rate was significantly decreased，and the secretion of ColⅣ and FN were decreased，and the differences were statistically significant（P < 0.05）. Conclusion BKCa was highly expressed in DN cell models induced by high glucose，and cell proliferation rate，ColⅣ and FN secretion were significantly reduced after BKCa inhibition，thus improving DN lesions. This effect was related to TGF- β1/Smad2/3 signaling pathway.

关键词

糖尿病肾病大电导钙激活钾通道胶原Ⅳ纤连蛋白TGF-β1Smad2/3

Keywords

Diabetic nephropathyBKCaColⅣFNTGF-β1Smad2/3

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