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TangShenWeiNing Formula Prevents Diabetic Nephropathy by Protecting Podocytes Through the SIRT1/HIF-1α Pathway

BACKGROUND: Diabetic nephropathy (DN) represents a major complication of diabetes, and podocyte injury has a critical function in DN development. TangShenWeiNing formula (TSWN) has been demonstrated to efficiently decrease proteinuria and protect podocytes in DN. This work aimed to explore the mecha...

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Autores principales: Chang, Jing, Zheng, Jinsu, Gao, Xia, Dong, Hengbei, Yu, Haitian, Huang, Mengxiu, Sun, Zhencheng, Feng, Xiaomeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204479/
https://www.ncbi.nlm.nih.gov/pubmed/35721758
http://dx.doi.org/10.3389/fendo.2022.888611
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author Chang, Jing
Zheng, Jinsu
Gao, Xia
Dong, Hengbei
Yu, Haitian
Huang, Mengxiu
Sun, Zhencheng
Feng, Xiaomeng
author_facet Chang, Jing
Zheng, Jinsu
Gao, Xia
Dong, Hengbei
Yu, Haitian
Huang, Mengxiu
Sun, Zhencheng
Feng, Xiaomeng
author_sort Chang, Jing
collection PubMed
description BACKGROUND: Diabetic nephropathy (DN) represents a major complication of diabetes, and podocyte injury has a critical function in DN development. TangShenWeiNing formula (TSWN) has been demonstrated to efficiently decrease proteinuria and protect podocytes in DN. This work aimed to explore the mechanism by which TSWN alleviates DN and protects podocytes. METHODS: The major bioactive components of TSWN were detected by mass spectrometry (MS) and pharmacological databases. Eight-week-old male C57BLKS/J db/m and db/db mice were provided pure water, valsartan, low dose TSWN, middle dose TSWN and high dose TSWN by gavage for 12 weeks, respectively. RESULTS: MS and network pharmacology analyses suggested that TSWN might prevent DN through the sirtuin (SIRT)1/hypoxia-inducible factor (HIF)-1α pathway. Diabetic mice showed elevated urinary albumin in comparison with non-diabetic mice, and TSWN decreased urinary albumin in diabetic mice. Histological injury increased in the kidney in diabetic mice, which could be improved by TSWN. Fibrosis and collagen I expression were induced in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney; TSWN alleviated these effects. Apoptosis and cleaved caspase-3 were induced in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney, and TSWN blunted these effects. Podocytes were damaged in the diabetic mouse kidney, which was improved by TSWN. Podocin and nephrin amounts were decreased in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney, and podocalyxin was increased in urine of diabetic animals in comparison with non-diabetic counterparts. After TSWN treatment, podocin and nephrin were raised in the diabetic mouse kidney, and urinary podocalyxin was depressed in diabetic animals. Diabetic mice had lower SIRT1 and higher HIF-1α amounts in kidney specimens in comparison with non-diabetic mice, and TSWN promoted SIRT1 and inhibited HIF-1α in the diabetic mouse kidney. Moreover, co-staining of SIRT1 and podocin revealed that SIRT1 decreased in podocytes from diabetic mice in comparison with those from non-diabetic mice, and TSWN elevated SIRT1 in podocytes. CONCLUSIONS: This study indicated that TSWN alleviates DN by improving podocyte injury through the SIRT1/HIF-1α pathway in diabetic mouse kidneys.
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spelling pubmed-92044792022-06-18 TangShenWeiNing Formula Prevents Diabetic Nephropathy by Protecting Podocytes Through the SIRT1/HIF-1α Pathway Chang, Jing Zheng, Jinsu Gao, Xia Dong, Hengbei Yu, Haitian Huang, Mengxiu Sun, Zhencheng Feng, Xiaomeng Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Diabetic nephropathy (DN) represents a major complication of diabetes, and podocyte injury has a critical function in DN development. TangShenWeiNing formula (TSWN) has been demonstrated to efficiently decrease proteinuria and protect podocytes in DN. This work aimed to explore the mechanism by which TSWN alleviates DN and protects podocytes. METHODS: The major bioactive components of TSWN were detected by mass spectrometry (MS) and pharmacological databases. Eight-week-old male C57BLKS/J db/m and db/db mice were provided pure water, valsartan, low dose TSWN, middle dose TSWN and high dose TSWN by gavage for 12 weeks, respectively. RESULTS: MS and network pharmacology analyses suggested that TSWN might prevent DN through the sirtuin (SIRT)1/hypoxia-inducible factor (HIF)-1α pathway. Diabetic mice showed elevated urinary albumin in comparison with non-diabetic mice, and TSWN decreased urinary albumin in diabetic mice. Histological injury increased in the kidney in diabetic mice, which could be improved by TSWN. Fibrosis and collagen I expression were induced in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney; TSWN alleviated these effects. Apoptosis and cleaved caspase-3 were induced in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney, and TSWN blunted these effects. Podocytes were damaged in the diabetic mouse kidney, which was improved by TSWN. Podocin and nephrin amounts were decreased in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney, and podocalyxin was increased in urine of diabetic animals in comparison with non-diabetic counterparts. After TSWN treatment, podocin and nephrin were raised in the diabetic mouse kidney, and urinary podocalyxin was depressed in diabetic animals. Diabetic mice had lower SIRT1 and higher HIF-1α amounts in kidney specimens in comparison with non-diabetic mice, and TSWN promoted SIRT1 and inhibited HIF-1α in the diabetic mouse kidney. Moreover, co-staining of SIRT1 and podocin revealed that SIRT1 decreased in podocytes from diabetic mice in comparison with those from non-diabetic mice, and TSWN elevated SIRT1 in podocytes. CONCLUSIONS: This study indicated that TSWN alleviates DN by improving podocyte injury through the SIRT1/HIF-1α pathway in diabetic mouse kidneys. Frontiers Media S.A. 2022-05-26 /pmc/articles/PMC9204479/ /pubmed/35721758 http://dx.doi.org/10.3389/fendo.2022.888611 Text en Copyright © 2022 Chang, Zheng, Gao, Dong, Yu, Huang, Sun and Feng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Chang, Jing
Zheng, Jinsu
Gao, Xia
Dong, Hengbei
Yu, Haitian
Huang, Mengxiu
Sun, Zhencheng
Feng, Xiaomeng
TangShenWeiNing Formula Prevents Diabetic Nephropathy by Protecting Podocytes Through the SIRT1/HIF-1α Pathway
title TangShenWeiNing Formula Prevents Diabetic Nephropathy by Protecting Podocytes Through the SIRT1/HIF-1α Pathway
title_full TangShenWeiNing Formula Prevents Diabetic Nephropathy by Protecting Podocytes Through the SIRT1/HIF-1α Pathway
title_fullStr TangShenWeiNing Formula Prevents Diabetic Nephropathy by Protecting Podocytes Through the SIRT1/HIF-1α Pathway
title_full_unstemmed TangShenWeiNing Formula Prevents Diabetic Nephropathy by Protecting Podocytes Through the SIRT1/HIF-1α Pathway
title_short TangShenWeiNing Formula Prevents Diabetic Nephropathy by Protecting Podocytes Through the SIRT1/HIF-1α Pathway
title_sort tangshenweining formula prevents diabetic nephropathy by protecting podocytes through the sirt1/hif-1α pathway
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204479/
https://www.ncbi.nlm.nih.gov/pubmed/35721758
http://dx.doi.org/10.3389/fendo.2022.888611
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