TWEAK/Fn14 mediates atrial-derived HL-1 myocytes hypertrophy via JAK2/STAT3 signalling pathway

Li Hao; Manyi Ren; Bing Rong; Fei Xie; Ming-Jie Lin; Ya-Chao Zhao; Xin Yue; Wen-Qiang Han; Jing-Quan Zhong

doi:10.1111/jcmm.13724

TWEAK/Fn14 mediates atrial-derived HL-1 myocytes hypertrophy via JAK2/STAT3 signalling pathway

J Cell Mol Med. 2018 Sep;22(9):4344-4353. doi: 10.1111/jcmm.13724. Epub 2018 Jul 4.

Authors

Li Hao¹, Manyi Ren^{1

2}, Bing Rong¹, Fei Xie¹, Ming-Jie Lin¹, Ya-Chao Zhao¹, Xin Yue¹, Wen-Qiang Han¹, Jing-Quan Zhong¹

Affiliations

¹ The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
² Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.

Abstract

Atrial myocyte hypertrophy is one of the most important substrates in the development of atrial fibrillation (AF). The TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy in cardiomyopathy. This study therefore investigated the effects of Fn14 on atrial hypertrophy and underlying cellular mechanisms using HL-1 atrial myocytes. In patients with AF, Fn14 protein levels were higher in atrial myocytes from atrial appendages, and expression of TWEAK was increased in peripheral blood mononuclear cells, while TWEAK serum levels were decreased. In vitro, Fn14 expression was up-regulated in response to TWEAK treatment in HL-1 atrial myocytes. TWEAK increased the expression of ANP and Troponin T, and Fn14 knockdown counteracted the effect. Inhibition of JAK2, STAT3 by specific siRNA attenuated TWEAK-induced HL-1 atrial myocytes hypertrophy. In conclusion, TWEAK/Fn14 axis mediates HL-1 atrial myocytes hypertrophy partly through activation of the JAK2/STAT3 pathway.

Keywords: Fn14; HL-1 atrial myocytes; JAK2/STAT3; TWEAK; hypertrophy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Animals
Atrial Fibrillation / genetics*
Atrial Fibrillation / metabolism
Atrial Fibrillation / pathology
Atrial Natriuretic Factor / genetics
Atrial Natriuretic Factor / metabolism
Cardiomegaly / genetics*
Cardiomegaly / metabolism
Cardiomegaly / pathology
Case-Control Studies
Cytokine TWEAK / genetics*
Cytokine TWEAK / metabolism
Disease Models, Animal
Female
Gene Expression Regulation
Heart Atria / metabolism
Heart Atria / pathology
Humans
Janus Kinase 2 / antagonists & inhibitors
Janus Kinase 2 / genetics*
Janus Kinase 2 / metabolism
Leukocytes, Mononuclear / metabolism
Leukocytes, Mononuclear / pathology
Male
Mice
Middle Aged
Myocytes, Cardiac / metabolism*
Myocytes, Cardiac / pathology
Primary Cell Culture
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
STAT3 Transcription Factor / antagonists & inhibitors
STAT3 Transcription Factor / genetics*
STAT3 Transcription Factor / metabolism
Signal Transduction
TWEAK Receptor / antagonists & inhibitors
TWEAK Receptor / genetics*
TWEAK Receptor / metabolism
Troponin T / genetics
Troponin T / metabolism

Substances

Cytokine TWEAK
RNA, Small Interfering
STAT3 Transcription Factor
Stat3 protein, mouse
TWEAK Receptor
Tnfrsf12a protein, mouse
Tnfsf12 protein, mouse
Troponin T
Atrial Natriuretic Factor
Jak2 protein, mouse
Janus Kinase 2