miR-221-5p-Mediated Downregulation of JNK2 Aggravates Acute Lung Injury.

Autor:	Yang J; Department of Surgery, College of Medicine and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, United States., Do-Umehara HC; Department of Surgery, College of Medicine and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, United States., Zhang Q; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States., Wang H; Department of Surgery, College of Medicine and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, United States., Hou C; Department of Surgery, College of Medicine and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, United States., Dong H; Department of Surgery, College of Medicine and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, United States., Perez EA; Department of Surgery, College of Medicine and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, United States., Sala MA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States., Anekalla KR; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States., Walter JM; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States., Liu S; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China., Wunderink RG; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.; Simpson Querrey Institute for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States., Budinger GRS; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States., Liu J; Department of Surgery, College of Medicine and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Nov 25; Vol. 12, pp. 700933. Date of Electronic Publication: 2021 Nov 25 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.700933
Abstrakt:	Sepsis and acute lung injury (ALI) are linked to mitochondrial dysfunction; however, the underlying mechanism remains elusive. We previously reported that c-Jun N-terminal protein kinase 2 (JNK2) promotes stress-induced mitophagy by targeting small mitochondrial alternative reading frame (smARF) for ubiquitin-mediated proteasomal degradation, thereby preventing mitochondrial dysfunction and restraining inflammasome activation. Here we report that loss of JNK2 exacerbates lung inflammation and injury during sepsis and ALI in mice. JNK2 is downregulated in mice with endotoxic shock or ALI, concomitantly correlated inversely with disease severity. Small RNA sequencing revealed that miR-221-5p, which contains seed sequence matching to JNK2 mRNA 3' untranslated region (3'UTR), is upregulated in response to lipopolysaccharide, with dynamically inverse correlation with JNK2 mRNA levels. miR-221-5p targets the 3'UTR of JNK2 mRNA leading to its downregulation. Accordingly, miR-221-5p exacerbates lung inflammation and injury during sepsis in mice by targeting JNK2. Importantly, in patients with pneumonia in medical intensive care unit, JNK2 mRNA levels in alveolar macrophages flow sorted from non-bronchoscopic broncholaveolar lavage (BAL) fluid were inversely correlated strongly and significantly with the percentage of neutrophils, neutrophil and white blood cell counts in BAL fluid. Our data suggest that miR-221-5p targets JNK2 and thereby aggravates lung inflammation and injury during sepsis. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Yang, Do-Umehara, Zhang, Wang, Hou, Dong, Perez, Sala, Anekalla, Walter, Liu, Wunderink, Budinger and Liu.)
Databáze:	MEDLINE
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