Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition

Xiaohong Quan,1,* Huihui Liu,1,* Dongmei Ye,2 Xinling Ding,3 Xiulan Su4 1Experiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 2Core Facility Center for Functional Experimen...

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Autores principales:	Quan X, Liu H, Ye D, Ding X, Su X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	diabetic nephropathy high glucose oxidative stress inflammation apoptosis Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/46ae4318f8a14c42859552a49bdf6f06
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spelling	oai:doaj.org-article:46ae4318f8a14c42859552a49bdf6f062021-12-02T14:51:56ZForsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition1178-7007https://doaj.org/article/46ae4318f8a14c42859552a49bdf6f062021-04-01T00:00:00Zhttps://www.dovepress.com/forsythoside-a-alleviates-high-glucose-induced-oxidative-stress-and-in-peer-reviewed-fulltext-article-DMSOhttps://doaj.org/toc/1178-7007Xiaohong Quan,1,* Huihui Liu,1,* Dongmei Ye,2 Xinling Ding,3 Xiulan Su4 1Experiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 2Core Facility Center for Functional Experiments, CUSBMS, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 3Department of Human Anatomy, CUSBMS, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 4Clinical Research Center for Medical Sciences, IMMU, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohong QuanExperiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, No. 1 Yingbin Road, Chifeng City, Inner Mongolia, 024000, People’s Republic of ChinaEmail quanxiaohongxh@163.comBackground: Podocyte injury serves an important role during the progression of diabetic nephropathy (DN). The aim of this study was to investigate the effects of forsythoside A (FA) on high glucose (HG)-induced podocyte injury and to identify the possible mechanisms.Methods: MPC-5 podocytes were cultured under HG conditions. After exposure to different doses of FA, cell viability and apoptosis were respectively evaluated with CCK-8 assay and flow cytometry. Then, the levels of oxidative stress-related markers and inflammatory factors were examined by corresponding kits. Western blot analysis was employed to detect the expression of Nox2, Nox4, COX-2, iNOS and matrix metalloproteinases 12 (MMP12). Subsequently, MMP12 was overexpressed to assess whether the effects of FA on HG-stimulated podocyte injury were mediated by MMP12 and MAPK signaling.Results: Results indicated that FA dose-dependently elevated cell viability, reduced cell apoptosis in HG-induced MPC-5 cells. Additionally, FA significantly inhibited oxidative stress, which could be certified by decreased content of malondialdehyde (MDA), enhanced activities of superoxide dismutase (SOD) and catalase (CAT), and downregulated expression of Nox2 and Nox4. Moreover, notably reduced levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were observed in FA-treated MPC-5 cells under HG conditions, accompanied by decreased COX-2 and iNOS expression. Remarkably, FA suppressed MMP12 expression in a dose-dependent manner, and the effects of FA on MPC-5 cells exposed to HG were partially counteracted by MMP12 overexpression. Mechanically, FA inactivated the expression of phospho-ERK (p-ERK), p-p38 and p-JNK, which was restored after MMP12 overexpression.Conclusion: These findings demonstrate a protective mechanism of FA by inactivating MAPK signaling via MMP12 inhibition in HG-induced podocyte injury, providing a promising therapeutic candidate for the treatment of DN.Keywords: diabetic nephropathy, high glucose, oxidative stress, inflammation, apoptosisQuan XLiu HYe DDing XSu XDove Medical Pressarticlediabetic nephropathyhigh glucoseoxidative stressinflammationapoptosisSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 1885-1895 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetic nephropathy high glucose oxidative stress inflammation apoptosis Specialties of internal medicine RC581-951
spellingShingle	diabetic nephropathy high glucose oxidative stress inflammation apoptosis Specialties of internal medicine RC581-951 Quan X Liu H Ye D Ding X Su X Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition
description	Xiaohong Quan,1,* Huihui Liu,1,* Dongmei Ye,2 Xinling Ding,3 Xiulan Su4 1Experiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 2Core Facility Center for Functional Experiments, CUSBMS, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 3Department of Human Anatomy, CUSBMS, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 4Clinical Research Center for Medical Sciences, IMMU, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohong QuanExperiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, No. 1 Yingbin Road, Chifeng City, Inner Mongolia, 024000, People’s Republic of ChinaEmail quanxiaohongxh@163.comBackground: Podocyte injury serves an important role during the progression of diabetic nephropathy (DN). The aim of this study was to investigate the effects of forsythoside A (FA) on high glucose (HG)-induced podocyte injury and to identify the possible mechanisms.Methods: MPC-5 podocytes were cultured under HG conditions. After exposure to different doses of FA, cell viability and apoptosis were respectively evaluated with CCK-8 assay and flow cytometry. Then, the levels of oxidative stress-related markers and inflammatory factors were examined by corresponding kits. Western blot analysis was employed to detect the expression of Nox2, Nox4, COX-2, iNOS and matrix metalloproteinases 12 (MMP12). Subsequently, MMP12 was overexpressed to assess whether the effects of FA on HG-stimulated podocyte injury were mediated by MMP12 and MAPK signaling.Results: Results indicated that FA dose-dependently elevated cell viability, reduced cell apoptosis in HG-induced MPC-5 cells. Additionally, FA significantly inhibited oxidative stress, which could be certified by decreased content of malondialdehyde (MDA), enhanced activities of superoxide dismutase (SOD) and catalase (CAT), and downregulated expression of Nox2 and Nox4. Moreover, notably reduced levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were observed in FA-treated MPC-5 cells under HG conditions, accompanied by decreased COX-2 and iNOS expression. Remarkably, FA suppressed MMP12 expression in a dose-dependent manner, and the effects of FA on MPC-5 cells exposed to HG were partially counteracted by MMP12 overexpression. Mechanically, FA inactivated the expression of phospho-ERK (p-ERK), p-p38 and p-JNK, which was restored after MMP12 overexpression.Conclusion: These findings demonstrate a protective mechanism of FA by inactivating MAPK signaling via MMP12 inhibition in HG-induced podocyte injury, providing a promising therapeutic candidate for the treatment of DN.Keywords: diabetic nephropathy, high glucose, oxidative stress, inflammation, apoptosis
format	article
author	Quan X Liu H Ye D Ding X Su X
author_facet	Quan X Liu H Ye D Ding X Su X
author_sort	Quan X
title	Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition
title_short	Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition
title_full	Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition
title_fullStr	Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition
title_full_unstemmed	Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition
title_sort	forsythoside a alleviates high glucose-induced oxidative stress and inflammation in podocytes by inactivating mapk signaling via mmp12 inhibition
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/46ae4318f8a14c42859552a49bdf6f06
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_version_	1718389443766779904

Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition

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