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Integrin αvβ5 inhibition protects against ischemia-reperfusion-induced lung injury in an autophagy-dependent manner.
. 2017 08 01; 313(2):L384-L394.

Abstract

Integrin αvβ5 mediates pulmonary endothelial barrier function and acute lung injury (LI), but its roles in cell apoptosis and autophagy are unclear. Thus, the aims of this study were to investigate the significance of αvβ5 in ischemia-reperfusion (I/R)-induced apoptosis and LI and to explore the relationship between αvβ5 and autophagy. Human pulmonary microvascular endothelial cells (HPMVECs) were pretreated with an αvβ5-blocking antibody (ALULA) and challenged with oxygen-glucose deprivation/oxygen-glucose restoration, which mimics I/R; then, cellular autophagy and apoptosis were detected, and cell permeability was assessed. In vivo, mice were pretreated with the autophagy inhibitor chloroquine (CLQ), followed by treatment with ALULA. The mice then underwent operative lung I/R. LI was assessed by performing a pathological examination, calculating the wet/dry lung weight ratio and detecting the bronchial alveolar lavage fluid (BALF) protein concentration. αvβ5 inhibition promoted HPMVEC autophagy under I/R in vitro, alleviated cell permeability, decreased the apoptosis ratio, and activated caspase-3 expression. These outcomes were significantly diminished when autophagy was inhibited with a small-interfering RNA construct targeting autophagy-related gene 7 (siATG7). Moreover, ALULA pretreatment alleviated I/R-induced LI (I/R-LI), which manifested as a decreased wet/dry lung weight ratio, an altered BALF protein concentration, and lung edema. Preinhibiting autophagy with CLQ, however, eliminated the protective effects of ALULA on I/R-LI. Therefore, inhibiting αvβ5 effectively ameliorated I/R-induced endothelial cell apoptosis and I/R-LI. This process was dependent on improved autophagy and its inhibitory effects on activated caspase-3.

Authors+Show Affiliations

Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, China.Department of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, China.Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. Shanghai Respiratory Research Institute, Shanghai, China; and.Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. Shanghai Respiratory Research Institute, Shanghai, China; and.Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, China.Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. Shanghai Respiratory Research Institute, Shanghai, China; and.Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; cxbai@fudan.edu.cn. Shanghai Respiratory Research Institute, Shanghai, China; and. State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28522565

Citation

Zhang, Dan, et al. "Integrin Αvβ5 Inhibition Protects Against Ischemia-reperfusion-induced Lung Injury in an Autophagy-dependent Manner." American Journal of Physiology. Lung Cellular and Molecular Physiology, vol. 313, no. 2, 2017, pp. L384-L394.
Zhang D, Li C, Song Y, et al. Integrin αvβ5 inhibition protects against ischemia-reperfusion-induced lung injury in an autophagy-dependent manner. Am J Physiol Lung Cell Mol Physiol. 2017;313(2):L384-L394.
Zhang, D., Li, C., Song, Y., Zhou, J., Li, Y., Li, J., & Bai, C. (2017). Integrin αvβ5 inhibition protects against ischemia-reperfusion-induced lung injury in an autophagy-dependent manner. American Journal of Physiology. Lung Cellular and Molecular Physiology, 313(2), L384-L394. https://doi.org/10.1152/ajplung.00391.2016
Zhang D, et al. Integrin Αvβ5 Inhibition Protects Against Ischemia-reperfusion-induced Lung Injury in an Autophagy-dependent Manner. Am J Physiol Lung Cell Mol Physiol. 2017 08 1;313(2):L384-L394. PubMed PMID: 28522565.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Integrin αvβ5 inhibition protects against ischemia-reperfusion-induced lung injury in an autophagy-dependent manner. AU - Zhang,Dan, AU - Li,Chichi, AU - Song,Yuanlin, AU - Zhou,Jian, AU - Li,Yuping, AU - Li,Jing, AU - Bai,Chunxue, Y1 - 2017/05/18/ PY - 2016/09/08/received PY - 2017/04/03/revised PY - 2017/05/16/accepted PY - 2017/5/20/pubmed PY - 2017/8/30/medline PY - 2017/5/20/entrez KW - apoptosis KW - autophagy KW - integrin αvβ5 KW - lung injury KW - lung ischemia-reperfusion KW - oxygen-glucose deprivation/oxygen-glucose restoration KW - pulmonary microvascular endothelial cells SP - L384 EP - L394 JF - American journal of physiology. Lung cellular and molecular physiology JO - Am. J. Physiol. Lung Cell Mol. Physiol. VL - 313 IS - 2 N2 - Integrin αvβ5 mediates pulmonary endothelial barrier function and acute lung injury (LI), but its roles in cell apoptosis and autophagy are unclear. Thus, the aims of this study were to investigate the significance of αvβ5 in ischemia-reperfusion (I/R)-induced apoptosis and LI and to explore the relationship between αvβ5 and autophagy. Human pulmonary microvascular endothelial cells (HPMVECs) were pretreated with an αvβ5-blocking antibody (ALULA) and challenged with oxygen-glucose deprivation/oxygen-glucose restoration, which mimics I/R; then, cellular autophagy and apoptosis were detected, and cell permeability was assessed. In vivo, mice were pretreated with the autophagy inhibitor chloroquine (CLQ), followed by treatment with ALULA. The mice then underwent operative lung I/R. LI was assessed by performing a pathological examination, calculating the wet/dry lung weight ratio and detecting the bronchial alveolar lavage fluid (BALF) protein concentration. αvβ5 inhibition promoted HPMVEC autophagy under I/R in vitro, alleviated cell permeability, decreased the apoptosis ratio, and activated caspase-3 expression. These outcomes were significantly diminished when autophagy was inhibited with a small-interfering RNA construct targeting autophagy-related gene 7 (siATG7). Moreover, ALULA pretreatment alleviated I/R-induced LI (I/R-LI), which manifested as a decreased wet/dry lung weight ratio, an altered BALF protein concentration, and lung edema. Preinhibiting autophagy with CLQ, however, eliminated the protective effects of ALULA on I/R-LI. Therefore, inhibiting αvβ5 effectively ameliorated I/R-induced endothelial cell apoptosis and I/R-LI. This process was dependent on improved autophagy and its inhibitory effects on activated caspase-3. SN - 1522-1504 UR - https://www.unboundmedicine.com/medline/citation/28522565/Integrin_αvβ5_inhibition_protects_against_ischemia_reperfusion_induced_lung_injury_in_an_autophagy_dependent_manner_ L2 - https://journals.physiology.org/doi/10.1152/ajplung.00391.2016?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -