Tangshen Formula Improves Diabetes-Associated Myocardial Fibrosis by Inhibiting TGF-β/Smads and Wnt/β-Catenin Pathways

被引：12
作者：
Hu, Lin [1 ,2 ]
Wang, Yuyang [1 ]
Wan, Yuzhou [1 ,3 ]
Ma, Liang [1 ]
Zhao, Tingting [1 ]
Li, Ping [1 ]
机构：
[1] China Japan Friendship Hosp, Beijing Key Lab Immune Mediated Inflammatory Dis, Inst Clin Med Sci, Beijing, Peoples R China
[2] Beijing Univ Chem Technol, Natl Energy R&D Ctr Biorefinery, Beijing, Peoples R China
[3] Weifang Med Univ, Coll Pharm, Weifang, Peoples R China
来源：
FRONTIERS IN MEDICINE | 2021年 / 8卷
基金：
北京市自然科学基金; 中国国家自然科学基金;
关键词：
Tangshen Formula; myocardial fibrosis; TGF-; beta; /Smad; Wnt/; -catenin; KKAy; MATRIX METALLOPROTEINASES; CARDIAC FIBROSIS; HEART-FAILURE; BETA-CATENIN; TGF-BETA-1; MECHANISMS; ACTIVATION;
D O I：
10.3389/fmed.2021.732042
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Cardiovascular disease has become the main cause of death among complications of diabetes. Myocardial fibrosis is a crucial pathological change of cardiovascular disease. Tangshen Formula (TSF) shows a good clinical effect in the treatment of diabetic kidney disease (DKD). However, whether TSF alleviates diabetes-associated myocardial fibrosis is still unknown. In the present research, we studied the effect and mechanism of TSF in the treatment of myocardial fibrosis in vivo and in vitro. We found that TSF treatment significantly downregulates myocardial fibrosis-related markers, including collagens I and III, and alpha-SMA. TSF also protects primary mouse cardiac fibroblast (CF) from transforming growth factor-beta 1- (TGF-beta 1-) induced damage. Moreover, TSF decreased the expression levels of TGF-beta/Smad-related genes (alpha-SMA, collagens I and III, TGF-beta 1, and pSmad2/3), and increased Smad7 gene expression. Finally, TSF decreased the expressions of wnt1, active-beta-catenin, FN, and MMP7 to regulate the Wnt/beta-catenin pathway. Taken together, TSF seems to attenuate myocardial fibrosis in KKAy mice by inhibiting TGF-beta/Smad2/3 and Wnt/beta-catenin signaling pathways.
引用
收藏
页数：13
相关论文
共 37 条
[1]   Quercetin prevents myocardial infarction adverse remodeling in rats by attenuating TGF-61/Smad3 signaling: Different mechanisms of action [J].
Albadrani, Ghadeer M. ;
BinMowyna, Mona N. ;
Bin-Jumah, May N. ;
El-Akabawy, Gehan ;
Aldera, Hussain ;
AL-Farga, Ammar M. .
SAUDI JOURNAL OF BIOLOGICAL SCIENCES, 2021, 28 (05) :2772-2782
[2]   Fibrosis of the left atria during progression of heart failure is associated with increased matrix metalloproteinases in the rat [J].
Boixel, C ;
Fontaine, V ;
Rücker-Martin, C ;
Milliez, P ;
Louedec, L ;
Michel, JB ;
Jacob, MP ;
Hatem, SN .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2003, 42 (02) :336-344
[3]   Melatonin alleviates cardiac fibrosis via inhibiting lncRNA MALAT1/miR-141-mediated NLRP3 inflammasome and TGF-β1/Smads signaling in diabetic cardiomyopathy [J].
Che, Hui ;
Wang, Yueqiu ;
Li, Hui ;
Li, Yang ;
Sahil, Abbas ;
Lv, Jie ;
Liu, Yining ;
Yang, Zhenyu ;
Dong, Ruixue ;
Xue, Hongru ;
Wang, Lihong .
FASEB JOURNAL, 2020, 34 (04) :5282-5298
[4]  
Chinese Pharmacopoeia Commission, 2015, PHARMACOPOEIA PEOPLE
[5]   Smad3 Signaling Critically Regulates Fibroblast Phenotype and Function in Healing Myocardial Infarction [J].
Dobaczewski, Marcin ;
Bujak, Marcin ;
Li, Na ;
Gonzalez-Quesada, Carlos ;
Mendoza, Leonardo H. ;
Wang, Xiao-Fan ;
Frangogiannis, Nikolaos G. .
CIRCULATION RESEARCH, 2010, 107 (03) :418-U176
[6]  
Espeland Torvald, 2018, Tidsskr Nor Laegeforen, V138, DOI 10.4045/tidsskr.17.1027
[7]   Potential Implications of Quercetin and its Derivatives in Cardioprotection [J].
Ferenczyova, Kristina ;
Kalocayova, Barbora ;
Bartekova, Monika .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (05)
[8]   An overview of the inflammatory signalling mechanisms in the myocardium underlying the development of diabetic cardiomyopathy [J].
Frati, Giacomo ;
Schirone, Leonardo ;
Chimenti, Isotta ;
Yee, Derek ;
Biondi-Zoccai, Giuseppe ;
Volpe, Massimo ;
Sciarretta, Sebastiano .
CARDIOVASCULAR RESEARCH, 2017, 113 (04) :378-388
[9]   Epidemiology of Diabetes Mellitus and Cardiovascular Disease [J].
Glovaci, Diana ;
Fan, Wenjun ;
Wong, Nathan D. .
CURRENT CARDIOLOGY REPORTS, 2019, 21 (04)
[10]   Wnt/β-Catenin Signaling: a Promising New Target for Fibrosis Diseases [J].
Guo, Y. ;
Xiao, L. ;
Sun, L. ;
Liu, F. .
PHYSIOLOGICAL RESEARCH, 2012, 61 (04) :337-346
1234