NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts.
10.4196/kjpp.2016.20.3.305
- Author:
Vu Thi THU
1
;
Hyoung Kyu KIM
;
Le Thanh LONG
;
To Thanh THUY
;
Nguyen Quang HUY
;
Soon Ha KIM
;
Nari KIM
;
Kyung Soo KO
;
Byoung Doo RHEE
;
Jin HAN
Author Information
1. National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea. phy
- Publication Type:Original Article
- Keywords:
Decorin;
Hypoxia/reoxygenation;
Infl ammation;
NecroX-5
- MeSH:
Animals;
Decorin;
Fibrosis;
Heart*;
Inflammation;
Liver;
Models, Theoretical;
Phosphorylation;
Rats*;
Reperfusion;
Reperfusion Injury;
Transforming Growth Factor beta;
Tumor Necrosis Factor-alpha
- From:The Korean Journal of Physiology and Pharmacology
2016;20(3):305-314
- CountryRepublic of Korea
- Language:English
-
Abstract:
Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating infl ammation and fi brosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 (10 µmol/L) treatment as experimental models. Addition of NecroX-5 signifi cantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 (TGFβ1) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, signifi cantly increased production of tumor necrosis factor alpha (TNFα), TGFβ1, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of TNFα, TGFβ1, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway.
