Isoliquiritigenin attenuates high glucose-induced proliferation, inflammation, and extracellular matrix deposition in glomerular mesangial cells by suppressing JAK2/STAT3 pathway.

التفاصيل البيبلوغرافية
العنوان:	Isoliquiritigenin attenuates high glucose-induced proliferation, inflammation, and extracellular matrix deposition in glomerular mesangial cells by suppressing JAK2/STAT3 pathway.
المؤلفون:	Zhang Z; Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, China., Deng S; Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, China., Shi Q; Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, China. qshi@zjut.edu.cn.
المصدر:	Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Jan; Vol. 397 (1), pp. 123-131. Date of Electronic Publication: 2023 Jun 27.
نوع المنشور:	Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0326264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1912 (Electronic) Linking ISSN: 00281298 NLM ISO Abbreviation: Naunyn Schmiedebergs Arch Pharmacol Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Berlin, New York, Springer Verlag.
مواضيع طبية MeSH:	Mesangial Cells* , Transforming Growth Factor beta1*/metabolism, Mice ; Animals ; Fibronectins ; Tumor Necrosis Factor-alpha/metabolism ; Glucose/metabolism ; Inflammation/drug therapy ; Inflammation/metabolism ; Cytokines/metabolism ; Cell Proliferation ; Extracellular Matrix/metabolism ; Collagen/metabolism
مستخلص:	To investigate the effect of isoliquiritigenin (ISL) on high glucose (HG)-induced glomerular mesangial cells (GMCs) proliferation, extracellular matrix (ECM) deposition and inflammation, and the underlying mechanisms. Mouse GMCs (SV40-MES-13) were cultured in HG medium, with or without ISL. The proliferation of GMCs was determined by MTT assay. The production of proinflammatory cytokines was detected by qRT-PCR and ELISA. The expression of connective tissue growth factor (CTGF), TGF-β1, collagen IV, and fibronectin was measured by qRT-PCR and western blot. The phosphorylation of JAK2 and STAT3 was examined by western blot. Next, JAK2 inhibitor AG490 was applied to HG-exposed GMCs. The levels of JAK2/STAT3 phosphorylation and pro-fibrotic markers were analyzed by western blot, and the secretion of TNF-α and IL-1β was evaluated by ELISA. GMCs were treated with HG, HG plus ISL or HG plus ISL, and recombinant IL-6 (rIL-6) which is a JAK2 activator. The levels of JAK2/STAT3 activation, ECM formation, and proinflammatory cytokines secretion were determined by western blot and ELISA, respectively. In mouse GMCs, ISL successfully repressed HG-induced hyperproliferation; production of TNF-α and IL-1β; expression of CTGF, TGF-β1, collagen IV, and fibronectin; and activation of JAK2/STAT3. Similar to ISL, AG490 was able to reverse the inflammation and ECM generation caused by HG. Moreover, rIL-6 impeded the amelioration of ISL on HG-induced adverse effects. Our study demonstrated that ISL displayed preventive effects on HG-exposed GMCs through inhibiting JAK2/STAT3 pathway and provided an insight into the application of ISL for diabetic nephropathy (DN) treatment. (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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معلومات مُعتمدة:	LY20C080003 Zhejiang Provincial Natural Science Foundation of China
فهرسة مساهمة:	Keywords: Diabetic nephropathy; Glomerular mesangial cells; Isoliquiritigenin; JAK2; STAT3
المشرفين على المادة:	0 (alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide) 0 (Transforming Growth Factor beta1) B9CTI9GB8F (isoliquiritigenin) 0 (Fibronectins) 0 (Tumor Necrosis Factor-alpha) IY9XDZ35W2 (Glucose) 0 (Cytokines) 9007-34-5 (Collagen)
تواريخ الأحداث:	Date Created: 20230627 Date Completed: 20240108 Latest Revision: 20240119
رمز التحديث:	20240119
DOI:	10.1007/s00210-023-02598-z
PMID:	37368032
قاعدة البيانات:	MEDLINE

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تدمد:	1432-1912
DOI:	10.1007/s00210-023-02598-z