Long Noncoding RNA: A Novel Insight into the Pathogenesis of Acute Lung Injury

Dutta, Saugata; Zhu, Yin; Han, Yohan; Almuntashiri, Sultan; Wang, Xiaoyun; Zhang, Duo

doi:10.3390/jcm12020604

Cited by 3 publications

(2 citation statements)

References 121 publications

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“…In severe cases, it may even lead to acute respiratory failure and death ( 2 ). According to reports, the incidence of ALI (~200,000 cases per year in the United States) and the overall mortality rate remain high, with ALI also being a prevalent cause of morbidity and mortality in critically ill patients ( 2 , 3 ). Although the understanding of the pathogenesis of ALI has improved, there is still no effective drug therapy to reduce the mortality rates of patients with ALI ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Targeted degradation of hexokinase 2 for anti‑inflammatory treatment in acute lung injury

Yang,

Dong,

Wang

et al. 2024

Mol Med Rep

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Acute lung injury (ALI) is an acute inflammatory lung disease associated with both innate and adaptive immune responses. Hexokinase 2 (HK2) is specifically highly expressed in numerous types of inflammation-related diseases and models. In the present study in vitro and in vivo effects of targeted degradation of HK2 on ALI were explored. The degradation of HK2 by the targeting peptide TAT (transactivator of transcription protein of HIV-1)-ataxin 1 (ATXN1)-chaperone-mediated autophagy-targeting motif (CTM) was demonstrated by ELISA and western blotting in vitro and in vivo . The inhibitory effects of TAT-ATXN1-CTM on lipopolysaccharide (LPS)-induced inflammatory responses were examined using ELISAs. The therapeutic effects of TAT-ATXN1-CTM on LPS-induced ALI were examined via histological examination and ELISAs in mice. 10 µM TAT-ATXN1-CTM administration decreased HK2 protein expression and the secretion of proinflammatory cytokines (TNF-α and IL-1β) without altering HK2 mRNA expression in LPS-treated both in vitro and in vivo , while pathological lung tissue damage and the accumulation of leukocytes, neutrophils, macrophages and lymphocytes in ALI were also significantly suppressed by 10 µM TAT-ATXN1-CTM treatment. TAT-ATXN1-CTM exhibited anti-inflammatory activity in vitro and decreased the severity of ALI in vivo . HK2 degradation may represent a novel therapeutic approach for ALI.

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Section: Introductionmentioning

confidence: 99%

Targeted degradation of hexokinase 2 for anti‑inflammatory treatment in acute lung injury

Yang,

Dong,

Wang

et al. 2024

Mol Med Rep

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“…Respiratory failure can also be the result of an acute lung injury (ALI) ( Dutta et al, 2023 ). Two original research articles here studied the two main pathophysiological aspects of the Acute lung injury (ALI): injury to the vascular endothelium and to alveolar epithelium.…”

mentioning

confidence: 99%

Editorial: Novel therapeutic strategies for the treatment of respiratory diseases

Di Vincenzo,

Ferraro,

Manca

et al. 2023

Front. Pharmacol.

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Deciphering regulatory patterns in a mouse model of hyperoxia-induced acute lung injury

Chen,

Liu,

Qin

et al. 2024

PeerJ

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Background Oxygen therapy plays a pivotal role in treating critically ill patients in the intensive care unit (ICU). However, excessive oxygen concentrations can precipitate hyperoxia, leading to damage in multiple organs, with a notable effect on the lungs. Hyperoxia condition may lead to hyperoxia-induced acute lung injury (HALI), deemed as a milder form of acute respiratory distress syndrome (ARDS). Given its clinical importance and practical implications, there is a compelling need to investigate the underlying pathogenesis and comprehensively understand the regulatory mechanisms implicated in the development of HALI Results In this study, we conducted a mouse model with HALI and performed regulatory mechanism analysis using RNA-seq on both HALI and control group. Comprehensive analysis revealed 727 genes of significant differential expression, including 248 long non-coding RNAs (lncRNAs). Also, alternative splicing events were identified from sequencing results. Notably, we observed up-regulation or abnormal alternative splicing of genes associated with immune response and ferroptosis under hyperoxia conditions. Utilizing weighted gene co-expression network analysis (WGCNA), we ascertained that genes involved in immune response formed a distinct cluster, showcasing an up-regulated pattern in hyperoxia, consistent with previous studies. Furthermore, a competing endogenous RNA (ceRNA) network was constructed, including 78 differentially expressed mRNAs and six differentially expressed lncRNAs, including H19. These findings uncover the intricate interplay of multiple transcriptional regulatory mechanisms specifically tailored to the pulmonary defense against HALI, substantiating the importance of these non-coding RNAs in this disease context. Conclusions Our results provide new insights into the potential mechanisms and underlying pathogenesis in the development of HALI at the post-transcriptional level. The findings of this study reveal potential regulatory interactions and biological roles of specific lncRNAs and genes, such as H19 and Sox9, encompassing driven gene expression patterns, alternative splicing events, and lncRNA-miRNA-mRNA ceRNA networks. These findings may pave the way for advancing therapeutic strategies and reducing the risk associated with oxygen treatment for patients.

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Long Noncoding RNA: A Novel Insight into the Pathogenesis of Acute Lung Injury

Cited by 3 publications

References 121 publications

Targeted degradation of hexokinase 2 for anti‑inflammatory treatment in acute lung injury

Targeted degradation of hexokinase 2 for anti‑inflammatory treatment in acute lung injury

Editorial: Novel therapeutic strategies for the treatment of respiratory diseases

Deciphering regulatory patterns in a mouse model of hyperoxia-induced acute lung injury

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