Erschienen in:
11.07.2022 | Original Research Article
Heme oxygenase-1 protects against endotoxin-induced acute lung injury depends on NAD+-mediated mitonuclear communication through PGC1α/PPARγ signaling pathway
verfasst von:
Simeng He, Jia Shi, Wenming Liu, Shihan Du, Yuan Zhang, Lirong Gong, Shuan Dong, Xiangyun Li, Qiaoying Gao, Jing Yang, Jianbo Yu
Erschienen in:
Inflammation Research
|
Ausgabe 9/2022
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Abstract
Endotoxin-induced acute lung injury (ALI) is a challenging life-threatening disease for which no specific therapy exists. Mitochondrial dysfunction is corroborated as hallmarks in sepsis which commonly disrupt mitochondria-centered cellular communication networks, especially mitonuclear crosstalk, where the ubiquitous cofactor nicotinamide adenine dinucleotide (NAD+) is essential for mitonuclear communication. Heme oxygenase-1 (HO-1) is critical for maintaining mitochondrial dynamic equilibrium and regulating endoplasmic reticulum (ER) and Golgi stress to alleviating acute lung injury. However, it is unclear whether HO-1 regulates NAD+-mediated mitonuclear communication to exert the endogenous protection during endotoxin-induced ALI. In this study, we observed HO-1 attenuated endotoxin-induced ALI by regulated NAD+ levels and NAD+ affected the mitonuclear communication, including mitonuclear protein imbalance and UPRmt to alleviate lung damage. We also found the protective effect of HO-1 depended on NAD+ and NAD+-mediated mitonuclear communication. Furtherly, the inhibition of the PGC1α/PPARγ signaling exacerbates the septic lung injury by reducing NAD+ levels and repressing the mitonuclear protein imbalance and UPRmt. Altogether, our study certified that HO-1 ameliorated endotoxin-induced acute lung injury by regulating NAD+ and NAD+-mediated mitonuclear communications through PGC1α/PPARγ pathway. The present study provided complementary evidence for the cytoprotective effect of HO-1 as a potential target for preventing and attenuating of endotoxin-induced ALI.