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Adiponectin ameliorates lung ischemia–reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats

BACKGROUND: Diabetes mellitus (DM) is a key contributing factor to poor survival in lung transplantation recipients. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of diabetic lung ischemia–reperfusion (IR) injury. The protective effects of adiponectin have been d...

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Autores principales: Jiang, Tao, Liu, Tianhua, Deng, Xijin, Ding, Wengang, Yue, Ziyong, Yang, Wanchao, Lv, Xiangqi, Li, Wenzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489101/
https://www.ncbi.nlm.nih.gov/pubmed/34602075
http://dx.doi.org/10.1186/s12931-021-01855-0
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author Jiang, Tao
Liu, Tianhua
Deng, Xijin
Ding, Wengang
Yue, Ziyong
Yang, Wanchao
Lv, Xiangqi
Li, Wenzhi
author_facet Jiang, Tao
Liu, Tianhua
Deng, Xijin
Ding, Wengang
Yue, Ziyong
Yang, Wanchao
Lv, Xiangqi
Li, Wenzhi
author_sort Jiang, Tao
collection PubMed
description BACKGROUND: Diabetes mellitus (DM) is a key contributing factor to poor survival in lung transplantation recipients. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of diabetic lung ischemia–reperfusion (IR) injury. The protective effects of adiponectin have been demonstrated in our previous study, but the underlying mechanism remains unclear. Here we demonstrated an important role of mitophagy in the protective effect of adiponectin during diabetic lung IR injury. METHODS: High-fat diet-fed streptozotocin-induced type 2 diabetic rats were exposed to adiponectin with or without administration of the SIRT1 inhibitor EX527 following lung transplantation. To determine the mechanisms underlying the action of adiponectin, rat pulmonary microvascular endothelial cells were transfected with SIRT1 small-interfering RNA or PINK1 small-interfering RNA and then subjected to in vitro diabetic lung IR injury. RESULTS: Mitophagy was impaired in diabetic lungs subjected to IR injury, which was accompanied by increased oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. Adiponectin induced mitophagy and attenuated subsequent diabetic lung IR injury by improving lung functional recovery, suppressing oxidative damage, diminishing inflammation, decreasing cell apoptosis, and preserving mitochondrial function. However, either administration of 3-methyladenine (3-MA), an autophagy antagonist or knockdown of PINK1 reduced the protective action of adiponectin. Furthermore, we demonstrated that APN affected PINK1 stabilization via the SIRT1 signaling pathway, and knockdown of SIRT1 suppressed PINK1 expression and compromised the protective effect of adiponectin. CONCLUSION: These data demonstrated that adiponectin attenuated reperfusion-induced oxidative stress, inflammation, apoptosis and mitochondrial dysfunction via activation of SIRT1- PINK1 signaling-mediated mitophagy in diabetic lung IR injury.
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spelling pubmed-84891012021-10-05 Adiponectin ameliorates lung ischemia–reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats Jiang, Tao Liu, Tianhua Deng, Xijin Ding, Wengang Yue, Ziyong Yang, Wanchao Lv, Xiangqi Li, Wenzhi Respir Res Research BACKGROUND: Diabetes mellitus (DM) is a key contributing factor to poor survival in lung transplantation recipients. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of diabetic lung ischemia–reperfusion (IR) injury. The protective effects of adiponectin have been demonstrated in our previous study, but the underlying mechanism remains unclear. Here we demonstrated an important role of mitophagy in the protective effect of adiponectin during diabetic lung IR injury. METHODS: High-fat diet-fed streptozotocin-induced type 2 diabetic rats were exposed to adiponectin with or without administration of the SIRT1 inhibitor EX527 following lung transplantation. To determine the mechanisms underlying the action of adiponectin, rat pulmonary microvascular endothelial cells were transfected with SIRT1 small-interfering RNA or PINK1 small-interfering RNA and then subjected to in vitro diabetic lung IR injury. RESULTS: Mitophagy was impaired in diabetic lungs subjected to IR injury, which was accompanied by increased oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. Adiponectin induced mitophagy and attenuated subsequent diabetic lung IR injury by improving lung functional recovery, suppressing oxidative damage, diminishing inflammation, decreasing cell apoptosis, and preserving mitochondrial function. However, either administration of 3-methyladenine (3-MA), an autophagy antagonist or knockdown of PINK1 reduced the protective action of adiponectin. Furthermore, we demonstrated that APN affected PINK1 stabilization via the SIRT1 signaling pathway, and knockdown of SIRT1 suppressed PINK1 expression and compromised the protective effect of adiponectin. CONCLUSION: These data demonstrated that adiponectin attenuated reperfusion-induced oxidative stress, inflammation, apoptosis and mitochondrial dysfunction via activation of SIRT1- PINK1 signaling-mediated mitophagy in diabetic lung IR injury. BioMed Central 2021-10-03 2021 /pmc/articles/PMC8489101/ /pubmed/34602075 http://dx.doi.org/10.1186/s12931-021-01855-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Jiang, Tao
Liu, Tianhua
Deng, Xijin
Ding, Wengang
Yue, Ziyong
Yang, Wanchao
Lv, Xiangqi
Li, Wenzhi
Adiponectin ameliorates lung ischemia–reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats
title Adiponectin ameliorates lung ischemia–reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats
title_full Adiponectin ameliorates lung ischemia–reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats
title_fullStr Adiponectin ameliorates lung ischemia–reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats
title_full_unstemmed Adiponectin ameliorates lung ischemia–reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats
title_short Adiponectin ameliorates lung ischemia–reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats
title_sort adiponectin ameliorates lung ischemia–reperfusion injury through sirt1-pink1 signaling-mediated mitophagy in type 2 diabetic rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489101/
https://www.ncbi.nlm.nih.gov/pubmed/34602075
http://dx.doi.org/10.1186/s12931-021-01855-0
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