Acute Hyperthermia Inhibits TGF-β1-induced Cardiac Fibroblast Activation via Suppression of Akt Signaling

被引：28

作者：

Narikawa, Masatoshi ^{[1
,2
]}

Umemura, Masanari ^{[1
,2
]}

Tanaka, Ryo ^{[1
,2
]}

Fujita, Takayuki ^{[1
,2
]}

Yokoyama, Utako ^{[1
]}

Ishigami, Tomoaki ^{[2
]}

Kimura, Kazuo ^{[2
]}

Tamura, Kouichi ^{[2
]}

Ishikawa, Yoshihiro ^{[1
]}

机构：

[1] Yokohama City Univ, Sch Med, Cardiovasc Res Inst, Yokohama, Kanagawa, Japan

[2] Yokohama City Univ, Sch Med, Med Sci & Cardiorenal Med, Yokohama, Kanagawa, Japan

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

MUSCLE ACTIN EXPRESSION; HEART-FAILURE; MYOCARDIAL FIBROSIS; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; DIASTOLIC DYSFUNCTION; CYTOKINES; MYOFIBROBLASTS; HYPERTROPHY; TRANSDIFFERENTIATION;

D O I：

10.1038/s41598-018-24749-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Transforming growth factor-beta 1 (TGF-beta 1) induces phenotypic changes in fibroblasts to become myofibroblasts with increased production of extracellular matrix (ECM) components and cytokines. It is also known that excessive activation of myofibroblasts accelerates cardiac fibrosis, remodeling, and thus cardiac dysfunction. However, no effective therapy has been established to prevent this process although recent clinical studies have demonstrated the effectiveness of hyperthermia in cardiac dysfunction. The aim of this study was to examine the molecular mechanism of hyperthermia on TGF-beta 1-mediated phenotypic changes in cardiac fibroblasts. TGF-beta 1 increased the expression of IL-6, alpha-smooth muscle actin (alpha-SMA), and collagen in human cardiac fibroblasts (HCFs). Hyperthermia (42 degrees C) significantly prevented these changes, i.e., increases in IL-6, alpha-SMA, and collagen, as induced by TGF-beta 1 in a time-dependent manner. Immunoblotting showed that hyperthermia decreased Akt/S6K signaling, but did not affect Smad2 and Smad3 signaling. Pharmacological inhibition of Akt signaling mimicked these effects of hyperthermia. Furthermore, hyperthermia treatment prevented cardiac fibrosis in Ang II infusion mice model. Putting together, our findings suggest that hyperthermia directly inhibits TGF-beta-mediated activation of HCFs via suppressing Akt/S6K signaling.

引用

页数：11

共 48 条

[1] Phosphatidylinositol 3-kinase function is required for transforming growth factor β-mediated epithelial to mesenchymal transition and cell migration [J].