New progress in the research on molecular mechanism of diabetic nephropathy

doi:10.3877/cma.j.issn.2095-3216.2021.02.006

Abstract

Abstract:

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes, and is the main cause of end-stage renal disease (ESRD). The pathogenesis of DN is complex, including glucose and lipid metabolism disorders, abnormal hemodynamics, oxidative stress, and inflammation. Recent studies have found that non-coding RNA, autophagy, pyroptosis, and exosomes, etc, play an important role in the development of DN. This article reviewed the latest research progress of the above molecular mechanisms in order to provide new insights on early diagnosis, individualized precision treatment, and delaying of DN progression.

Key words: Diabetic nephropathy, Non-coding RNA, Autophagy, Pyroptosis, Exosome

Zhirong Zhang, Weixia Han, Chen Wang. New progress in the research on molecular mechanism of diabetic nephropathy[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2021, 10(02): 90-95.

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References 36

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非编码RNA	参与DN的机制	举例	参考文献
miRNAs	氧化应激	miR-21、miR-25、miR-146a、miR-130b	[2,3]
	细胞凋亡	miR-33-5p、miR-20b、miR-134-5p、miR-21、miR-770-5p、miR-503 /E2F3轴、miR-424	[2,3]
	免疫炎症	miR-374a、miR-146a、miR-29b、miR-21、miR-874、miR-203、miR-141、miR-126	[2,3]
	细胞自噬	miR-155-5p、miR-192、miR-22、miR-18a-5p	[2,3]
	纤维化	miR-346、miR-23a、miR-34a-5p、miR-377、miR-27a、miR-302a-3p、miR-130b、miR-23b、miR-181a、miR-25、miR-133b、miR-199b、miR-451-5p、miR-16、miR-370、miR-184、miR-93	[2,3]
lncRNAs	参与肾小球足细胞损伤	MALAT1、lncRNA 01619、lncRNA ENSRNOG00000037522、PVT1、lncRNA SOX2OT	[3]
	参与肾小管上皮细胞损伤	MALAT1、MIAT	[3]
	参与肾小球系膜细胞的增殖、ECM积聚、纤维化	ENSMUST00000147869、CYP4B1-PS1-001、PVT1、lncRNA Tug1、lncRNA H2k2	[2,3]
	参与内质网应激、活性氧产生和炎性反应	MGC、Gm4419、ASncmtRNA2、MEG3、LRNA9884	[2]
circRNAs	参与肾小球系膜细胞ECM的积累	Circ-AKT3、circRNA _15698、circLRP6	[3]
	参与足细胞损伤	Circ_0000285	[4]
	参与细胞增殖和纤维化	Circ_0080425	[5]
	参与近端肾小管上皮细胞焦亡、炎症和纤维化	CircACTR2	[5]

非编码RNA	参与DN的机制	举例	参考文献
miRNAs	氧化应激	miR-21、miR-25、miR-146a、miR-130b	[2,3]
	细胞凋亡	miR-33-5p、miR-20b、miR-134-5p、miR-21、miR-770-5p、miR-503 /E2F3轴、miR-424	[2,3]
	免疫炎症	miR-374a、miR-146a、miR-29b、miR-21、miR-874、miR-203、miR-141、miR-126	[2,3]
	细胞自噬	miR-155-5p、miR-192、miR-22、miR-18a-5p	[2,3]
	纤维化	miR-346、miR-23a、miR-34a-5p、miR-377、miR-27a、miR-302a-3p、miR-130b、miR-23b、miR-181a、miR-25、miR-133b、miR-199b、miR-451-5p、miR-16、miR-370、miR-184、miR-93	[2,3]
lncRNAs	参与肾小球足细胞损伤	MALAT1、lncRNA 01619、lncRNA ENSRNOG00000037522、PVT1、lncRNA SOX2OT	[3]
	参与肾小管上皮细胞损伤	MALAT1、MIAT	[3]
	参与肾小球系膜细胞的增殖、ECM积聚、纤维化	ENSMUST00000147869、CYP4B1-PS1-001、PVT1、lncRNA Tug1、lncRNA H2k2	[2,3]
	参与内质网应激、活性氧产生和炎性反应	MGC、Gm4419、ASncmtRNA2、MEG3、LRNA9884	[2]
circRNAs	参与肾小球系膜细胞ECM的积累	Circ-AKT3、circRNA _15698、circLRP6	[3]
	参与足细胞损伤	Circ_0000285	[4]
	参与细胞增殖和纤维化	Circ_0080425	[5]
	参与近端肾小管上皮细胞焦亡、炎症和纤维化	CircACTR2	[5]

类别	炎症分子	在DN的作用机制	参考文献
转录因子	NFκB	JAK/STAT信号通路激活NF-κB，进而刺激促炎细胞因子、趋化因子和粘附分子的释放；NFκB上调MCP-1导致巨噬细胞浸润	[7，9]
	TGF-β1	TGF-β1/Smad3信号通路诱导系膜细胞产生ECM	[36]
促炎细胞因子	TNF-α	诱导炎症细胞的分化，对肾细胞的细胞毒性，激活细胞凋亡，改变肾小球血流动力学，增加血管内皮通透性和氧化应激	[9]
	IL-1	刺激前列腺素E产生和磷脂酶A2释放，参与肾小球血流动力学异常的发生	[9]
	IL-6	促进中性粒细胞浸润小管间质，影响细胞外基质动力学，促进肾小球基底膜增厚，足细胞肥大，与蛋白尿有关	[9]
	IL-18	刺激干扰素等细胞因子释放，增加粘附分子的表达，诱导内皮细胞凋亡	[9]
趋化因子	MCP-1/CCL2	在肾小管、间质巨噬细胞募集，足细胞减少，足突消失，肾小球基底膜断裂中发挥作用	[7，9]
黏附分子	ICAM-1	募集巨噬细胞，增加TNFα，NFκB对糖尿病的肾损伤	[7，9]
炎性小体	NLRP3炎性小体	参与巨噬细胞M1和M2极化	[7]

类别	炎症分子	在DN的作用机制	参考文献
转录因子	NFκB	JAK/STAT信号通路激活NF-κB，进而刺激促炎细胞因子、趋化因子和粘附分子的释放；NFκB上调MCP-1导致巨噬细胞浸润	[7，9]
	TGF-β1	TGF-β1/Smad3信号通路诱导系膜细胞产生ECM	[36]
促炎细胞因子	TNF-α	诱导炎症细胞的分化，对肾细胞的细胞毒性，激活细胞凋亡，改变肾小球血流动力学，增加血管内皮通透性和氧化应激	[9]
	IL-1	刺激前列腺素E产生和磷脂酶A2释放，参与肾小球血流动力学异常的发生	[9]
	IL-6	促进中性粒细胞浸润小管间质，影响细胞外基质动力学，促进肾小球基底膜增厚，足细胞肥大，与蛋白尿有关	[9]
	IL-18	刺激干扰素等细胞因子释放，增加粘附分子的表达，诱导内皮细胞凋亡	[9]
趋化因子	MCP-1/CCL2	在肾小管、间质巨噬细胞募集，足细胞减少，足突消失，肾小球基底膜断裂中发挥作用	[7，9]
黏附分子	ICAM-1	募集巨噬细胞，增加TNFα，NFκB对糖尿病的肾损伤	[7，9]
炎性小体	NLRP3炎性小体	参与巨噬细胞M1和M2极化	[7]

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