Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Τρίτη 21 Νοεμβρίου 2017

Heme Oxygenase 1 Attenuates Hypoxia-Reoxygenation Injury in Mice Liver Sinusoidal Endothelial Cells

ABSTRACT Background Heme oxygenase 1 (HO-1), a heat shock protein, can be involved in the resolution of inflammation by modulating cytokine expression and apoptotic cell death. Based on recent evidence that liver sinusoidal endothelial cells (LSECs) is the critical target in early period of liver ischemia-reperfusion injury (IRI), this study aims to clarify whether overexpression of HO-1 gene provides a protective effect on mice LSECs. Method LSECs were transfected with adenovirus vectors encoding mice HO-1 gene (Ad-HO-1) or green fluorescent protein (Ad-EGFP). Controls were not infected with any vector. LSECs were then treated with hypoxic or normoxic culture. We used low serum culture medium and hypoxia-reoxygenation (H-R) conditions to cause IRI in vitro. The transfection efficiency of HO-1 gene in LSECs, after 48 hours of transfection, and the effect of HO-1 on the model of H-R injury in LSECs were observed. Results Transfection of LSECs with Ad-HO-1 was at an optimal dose (MOI=80) to markedly express HO-1 mRNA and protein. Groups of overexpressed HO-1 showed lower levels of inflammatory factor mediators IL-6 and TNF-α. Survival rate of the cells after H-R injury was higher and attributed to overexpressed HO-1. In contrast, the control adenovirus expressing the EGFP failed to induce HO-1 expression, and stimulated cell apoptosis. HO-1 expression was down-regulated in all H-R groups compared to normoxia groups, which may be related to the disruption of the LSEC structure. Conclusion Up-regulation of HO-1 can attenuate H-R injury in LSECs by inhibiting proinflammatory cytokine release and diminishing apoptotic cell death. Corresponding author: Zhong Zeng, MD, PhD, Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical College, 295 Xichang Road, Kunming 650032, Yunnan Province, China. Telephone: +86-871-65359202; Fax: +86-871-65359202; Email: zzong@medmail.com.cn Authorship: Siming Qu, Bo Yuan, and Zhong Zeng contributed equally to this work; Siming Qu and Bo Yuan performed the majority of experiments; Hongbin Zhang participated in the performance of the research; Hanfei Huang participated in data analysis; Shikun Yang, Jie Lin, Li Jin, and Pu Wu participated in the writing of the paper. Disclosure: The authors declare no conflicts of interest. Funding: National Nature Science Foundation of China, No. 81660113 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2jMKTNS

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου

Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.