FGF2 isoforms play distinct roles in tubular epithelial-to-mesenchymal transition in diabetic nephropathy.
FGF2 isoforms play distinct roles in tubular epithelial-to-mesenchymal transition in diabetic nephropathy.
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DOI：
10.1016/j.yexcr.2022.113355
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发表时间：
2022-09
影响因子：
3.7
通讯作者：
Yingying Luo;Danfang Deng;Lamei Lin;Yikun Zhou;Lan Wang;X. Zou;Xiaoqin Wang
中科院分区：
文献类型：
--
作者：
Yingying Luo;Danfang Deng;Lamei Lin;Yikun Zhou;Lan Wang;X. Zou;Xiaoqin Wang
不同亚型的成纤维细胞生长因子-2(FGF2)在糖尿病肾病肾小管上皮向间充质转化(EMT)中的作用尚不清楚。本研究旨在探讨FGF2异构体在子宫内膜异位症发病机制中的作用。材料与方法采用免疫印迹和免疫荧光法检测FGF2异构体在db/db小鼠和高糖刺激的HK2细胞中的表达。结果高糖培养的HK2细胞和db/db小鼠肾脏中低相对分子质量(LMW)FGF2表达上调，而大分子FGF2表达下调。LMW FGF2过表达增强EMT，而HMW FGF2过表达减弱EMT。结论HMW-FGF2和LMW-FGF2在肾小管上皮细胞EMT过程中的表达和功能不同。低分子FGF2参与EMT，而HMW FGF2在EMT过程中起保护作用。
IntroductionThe role of different isoforms of Fibroblast growth factor-2 (FGF2) in tubular epithelial-to-mesenchymal transition (EMT) in diabetic nephropathy remains unknown. We aimed to evaluate the role of FGF2 isoforms in the pathogenesis of EMT.Materials and methodsWestern blot and immunofluorescence were used to assess the expression of FGF2 isoforms in db/db mice and high glucose-stimulated HK2 cells. The effects of specific FGF2 isoforms on EMT were explored via overexpression or knockdown of the corresponding isoform in HK2 cells cultivated in high glucose.ResultsExpression of low molecular weight (LMW) FGF2 was up-regulated while high molecular weight (HMW) FGF2 was down-regulated in the kidney of db/db mice and HK2 cells cultured in high glucose that underwent EMT. Overexpression of the LMW FGF2 enhanced EMT changes, while overexpression of the HMW FGF2 attenuated EMT. Knockdown of HMW FGF2 in HK2 cells promoted the EMT process.ConclusionsThe expression and function of LMW and HMW FGF2 differed in the process of EMT in tubular cells. LMW FGF2 contributed to EMT, while HMW FGF2 played a protective role in the EMT process.