Empagliflozin, a sodium glucose cotransporter-2 inhibitor, ameliorates peritoneal fibrosis via suppressing TGF-beta/Smad signaling

doi:10.1016/j.intimp.2021.107374

科研成果详情

题名	Empagliflozin, a sodium glucose cotransporter-2 inhibitor, ameliorates peritoneal fibrosis via suppressing TGF-beta/Smad signaling
作者	Shentu, Yangping 1; Li, Yuyang 2; Xie, Shicheng2; Jiang, Huanchang 2; Sun, Shicheng2; Lin, Rixu1; Chen, Chaosheng3; Bai, Yongheng4,5; Zhang, Yu 6; Zheng, Chenfei3; Zhou, Ying 3
发表日期	2021-04
发表期刊	INTERNATIONAL IMMUNOPHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Empagliflozin Peritoneal dialysis Sodium glucose transporter-2 Peritoneal fibrosis
其他关键词	MESOTHELIAL CELLS ; IN-VITRO ; HOMEOSTASIS ; PROMOTES ; DIALYSIS ; PATHWAY ; RATS
摘要	Sodium glucose cotransporter-2 (SGLT-2) inhibitor has been reported to exert a glucose-lowering effect in the peritoneum exposed to peritoneal dialysis solution. However, whether SGLT-2 inhibitors can regulate peritoneal fibrosis by suppressing TGF-beta/Smad signaling is unclear. We aimed to (i) examine the effect of the SGLT-2 inhibitor empagliflozin in reducing inflammatory reaction and preventing peritoneal dialysis solution-induced peritoneal fibrosis and (ii) elucidate the underlying mechanisms. High-glucose peritoneal dialysis solution or transforming growth factor beta 1 (TGF-beta 1) was used to induce peritoneal fibrosis in vivo, in a mouse peritoneal dialysis model (C57BL/6 mice) and in human peritoneal mesothelial cells in vitro, to stimulate extracellular matrix accumulation. The effects of empagliflozin and adeno-associated virus-RNAi, which is used to suppress SGLT-2 activity, on peritoneal fibrosis and extracellular matrix were evaluated. The mice that received chronic peritoneal dialysis solution infusions showed typical features of peritoneal fibrosis, including markedly increased peritoneal thickness, excessive matrix deposition, increased peritoneal permeability, and upregulated a-smooth muscle actin and collagen I expression. Empagliflozin treatment or downregulation of SGLT-2 expression significantly ameliorated these pathological changes. Inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6) and TGF beta/Smad signaling-associated proteins, such as TGF-beta 1 and phosphorylated Smad (p-Smad3), decreased in the empagliflozin-treated and SGLT-2 downregulated groups. In addition, empagliflozin treatment and down regulation of SGLT-2 expression reduced the levels of inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6), TGF-beta 1, alpha-smooth muscle actin, collagen I, and p-Smad3 accumulation in human peritoneal mesothelial cells. Collectively, these results indicated that empagliflozin exerted a clear protective effect on high-glucose peritoneal dialysis-induced peritoneal fibrosis via suppressing TGF-beta/Smad signaling.
资助项目	Natural Science Foundation of Zhejiang Province of ChinaNatural Science Foundation of Zhejiang Province [LQ19H050002, LQ19H080003, LY17H050005]; Wenzhou Municipal Science and Technology Bureau of China [ZS2017008, Y20180159, Y2020024]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31900685, 81772264]
出版者	ELSEVIER
出版地	AMSTERDAM
ISSN	1567-5769
EISSN	1878-1705
卷号	93 页码:107374
DOI	10.1016/j.intimp.2021.107374
页数	9
WOS类目	Immunology ; Pharmacology & Pharmacy
WOS研究方向	Immunology ; Pharmacology & Pharmacy
WOS记录号	WOS:000632487000002
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	33517222
SCOPUSEID	2-s2.0-85099972159
通讯作者地址	[Zheng, Chenfei]Department of Nephrology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
Scopus学科分类	Immunology and Allergy;Immunology;Pharmacology
TOP期刊	TOP期刊
引用统计	被引频次：8[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/14628
专题	附属第一医院第一临床医学院（信息与工程学院）、附属第一医院附属第一医院_肾内科
通讯作者	Zheng, Chenfei
作者单位	1.Department of Pathology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 3.Department of Nephrology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 4.Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 5.Institute of Kidney Health,Center for Health Assessment,Wenzhou Medical University,Wenzhou,325000,China; 6.Department of Hematology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 附属第一医院_肾内科
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Shentu, Yangping,Li, Yuyang,Xie, Shicheng,et al. Empagliflozin, a sodium glucose cotransporter-2 inhibitor, ameliorates peritoneal fibrosis via suppressing TGF-beta/Smad signaling[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2021,93:107374.
APA	Shentu, Yangping., Li, Yuyang., Xie, Shicheng., Jiang, Huanchang., Sun, Shicheng., ... & Zhou, Ying. (2021). Empagliflozin, a sodium glucose cotransporter-2 inhibitor, ameliorates peritoneal fibrosis via suppressing TGF-beta/Smad signaling. INTERNATIONAL IMMUNOPHARMACOLOGY, 93, 107374.
MLA	Shentu, Yangping,et al."Empagliflozin, a sodium glucose cotransporter-2 inhibitor, ameliorates peritoneal fibrosis via suppressing TGF-beta/Smad signaling".INTERNATIONAL IMMUNOPHARMACOLOGY 93(2021):107374.