NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNF alpha/Dcn/TGF beta 1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts

作者：Vu Thi Thu; Kim Hyoung Kyu; Le Thanh Long; To Thanh Thuy; Nguyen Quang Huy; Kim Soon Ha; Kim Nari; Ko Kyung Soo; Rhee Byoung Doo; Han Jin^*

来源：Korean Journal of Physiology and Pharmacology, 2016, 20(3): 305-314.

DOI：10.4196/kjpp.2016.20.3.305

• Decorin
• Hypoxia/reoxygenation
• Inflammation
• NecroX-5

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 inflammation and fibrosis 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 mu mol/L) treatment as experimental models. Addition of NecroX-5 significantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 (TGF beta 1) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, significantly increased production of tumor necrosis factor alpha (TNF alpha), TGF beta 1, 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 TNFa, TGF beta 1, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential anti-inflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the TN alpha F/Dcn/TGF beta 1/Smad2 pathway.

• 出版日期2016-5