Cigarette smoke extract induces airway epithelial cell death via repressing PRMT6/AKT signaling

Tiao Li; Kristen V Fanning; Toru Nyunoya; Yan Chen; Chunbin Zou

doi:10.18632/aging.202210

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Journal article

Cigarette smoke extract induces airway epithelial cell death via repressing PRMT6/AKT signaling

Tiao Li, Kristen V Fanning, Toru Nyunoya, Yan Chen and Chunbin Zou

Aging (Albany, NY.), Vol.12(23), pp.24301-24317

12/01/2020

DOI: 10.18632/aging.202210

PMID: 33260152

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Abstract

Chronic obstructive pulmonary disease (COPD) is a severe public health threat world-wide. Cigarette smoke (CS)-induced airway epithelial cell death is a major pathway of pathogenesis in emphysema, a subtype of COPD. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that catalyzes mono- and di-methylation on arginine residues within histone and non-histone proteins to modulate a variety of life processes, such as apoptosis. However, its role in CS-induced lung epithelial death has not been fully elucidated. Here we report that PRMT6 was decreased in mouse lung tissues from a cigarette smoke extract (CSE)-mediated experimental emphysematous model and in CSE treated or cigarette smoke exposed lung epithelial cells. Depletion of PRMT6 increased the protein levels of phosphatase PTEN and PI3K regulatory subunit p85 but decreased a downstream kinase PDK1, resulting in AKT dephosphorylation and thereafter, lung epithelial cell death. Knockout of PRMT6 inhibited epithelial survival and promoted CSE-mediated epithelial cell death, while ectopic expression of PRMT6 protein partially reversed epithelial cell death via PI3K/AKT-mediated cell survival signaling in CSE cellular models. These findings demonstrate that PRMT6 plays a crucial role in CS-induced bronchial epithelial cell death that may be a potential therapeutic target against the airway cell death in CS-induced COPD.

Animals

Cell Death - drug effects

Cell Line

Disease Models, Animal

Epithelial Cells - drug effects

Epithelial Cells - enzymology

Epithelial Cells - pathology

Humans

Lung - drug effects

Lung - enzymology

Lung - pathology

Mice, Inbred BALB C

Nuclear Proteins - genetics

Nuclear Proteins - metabolism

Phosphatidylinositol 3-Kinase - metabolism

Phosphorylation

Protein-Arginine N-Methyltransferases - genetics

Protein-Arginine N-Methyltransferases - metabolism

Proto-Oncogene Proteins c-akt - metabolism

PTEN Phosphohydrolase - metabolism

Pulmonary Emphysema - enzymology

Pulmonary Emphysema - etiology

Pulmonary Emphysema - pathology

Signal Transduction

Smoke - adverse effects

Tobacco Products - adverse effects

Details

Title: Subtitle: Cigarette smoke extract induces airway epithelial cell death via repressing PRMT6/AKT signaling
Creators: Tiao Li - University of Pittsburgh
Kristen V Fanning - University of Pittsburgh
Toru Nyunoya - University of Pittsburgh
Yan Chen - Central South University
Chunbin Zou - University of Pittsburgh
Resource Type: Journal article
Publication Details: Aging (Albany, NY.), Vol.12(23), pp.24301-24317
DOI: 10.18632/aging.202210
PMID: 33260152
ISSN: 1945-4589
eISSN: 1945-4589
Grant note: R01 HL142997 / NHLBI NIH HHS R01 HL125435 / NHLBI NIH HHS I01 CX000105 / CSRD VA
Language: English
Date published: 12/01/2020
Academic Unit: Internal Medicine
Record Identifier: 9985214105302771

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