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Toll-like receptor-6 (TLR6) deficient mice are protected from myocardial fibrosis induced by high fructose feeding through anti-oxidant and inflammatory signaling pathway.

Abstract：

:Diabetic cardiomyopathy is an essential complication of diabetes and characterized by persistent diastolic dysfunction, leading to myocardial fibrosis. Oxidative stress and inflammation lead to cell damage and are implicated in many disease states. In our study, we evaluated the effects of toll-like receptor 6 (TLR6) in cardiac remodeling. We established a mouse model of myocardial fibrosis with diabetes using 30% fructose. In comparison to HF-feeding control mice, TLR6 deficient mice developed less myocardial fibrosis with lower myocardial injury marker enzymes and AngII and aldosterone (ALD). In addition, Collagen type I/III, alpha smooth muscle-actin (α-SMA) and FSP-1, as typical markers of myocardial fibrosis formation, were found to be reduced due to TLR6 knockout in HF-induced mice. HF-feeding mice developed myocardial fibrosis with lower SOD activity, high level of MDA, O2(-) and H2O2 and increased serum pro-inflammatory cytokines, whereas TLR6 deficient mice after HF-administration were protected from myocardial fibrosis progression significantly. HF-feeding mice also displayed lower Nrf2 and higher XO levels, which was not observed in TLR6 deficient mice after HF-feeding. Furthermore, NF-κB pathway was inactivated for TLR6 knockout compared with HF-feeding mice. In vitro, fructose directly up-regulated α-SMA, TGF-β1, Collagen type I/III and FSP-1 via ROS production and NF-κB phosphorylation as well as pro-inflammatory cytokines releasing, which were inhibited for TLR6 deficiency. Taken together, TLR6 contributed to myocardial fibrosis progression, at least partly, through oxidative stress and inflammatory response, providing a potential therapeutic strategy for myocardial fibrosis treatment.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Zhang Y,Zhang Y

doi

10.1016/j.bbrc.2016.02.111

subject

Has Abstract

pub_date

2016-04-29 00:00:00

pages

388-95

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(16)30299-6

journal_volume

473

pub_type

杂志文章

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Toll-like receptor-6 (TLR6) deficient mice are protected from myocardial fibrosis induced by high fructose feeding through anti-oxidant and inflammatory signaling pathway.