IL-17A promotes lung fibrosis through impairing mitochondrial homeostasis in type II alveolar epithelial cells. 2022

Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, School of Clinical Medicine, Peking University, Beijing, China.

The dysfunction of type II alveolar epithelial cells (AECIIs), mainly manifested by apoptosis, has emerged as a major component of idiopathic pulmonary fibrosis (IPF) pathophysiology. A pivotal mechanism leading to AECIIs apoptosis is mitochondrial dysfunction. Recently, interleukin (IL)-17A has been demonstrated to have a pro-fibrotic role in IPF, though the mechanism is unclear. In this study, we report enhanced expression of IL-17 receptor A (IL-17RA) in AECIIs in lung samples of IPF patients, which may be related to the accumulation of mitochondria in AECIIs of IPF. Next, we investigated this relationship in bleomycin (BLM)-induced PF murine model. We found that IL-17A knockout (IL-17A-/- ) mice exhibited decreased apoptosis levels of AECIIs. This was possibly a result of the recovery of mitochondrial morphology from the improved mitochondrial dynamics of AECIIs, which eventually contributed to alleviating lung fibrosis. Analysis of in vitro data indicates that IL-17A impairs mitochondrial function and mitochondrial dynamics of mouse primary AECIIs, further promoting apoptosis. PTEN-induced putative kinase 1 (PINK1)/Parkin signal-mediated mitophagy is an important aspect of mitochondria homeostasis maintenance. Our data demonstrate that IL-17A inhibits mitophagy and promotes apoptosis of AECIIs by decreasing the expression levels of PINK1. We conclude that IL-17A exerts its pro-fibrotic effects by inducing mitochondrial dysfunction in AECIIs by disturbing mitochondrial dynamics and inhibiting PINK1-mediated mitophagy, thereby leading to apoptosis of AECIIs.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D011494 Protein Kinases A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. Protein Kinase,Kinase, Protein,Kinases, Protein
D001761 Bleomycin A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. BLEO-cell,Blanoxan,Blenoxane,Bleolem,Bleomicina,Bleomycin A(2),Bleomycin A2,Bleomycin B(2),Bleomycin B2,Bleomycin Sulfate,Bleomycins,Bleomycinum Mack,Bléomycine Bellon,BLEO cell,BLEOcell,Bellon, Bléomycine,Mack, Bleomycinum,Sulfate, Bleomycin
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005355 Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Cirrhosis,Fibroses
D006706 Homeostasis The processes whereby the internal environment of an organism tends to remain balanced and stable. Autoregulation
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054990 Idiopathic Pulmonary Fibrosis A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change. Cryptogenic Fibrosing Alveolitis,Familial Idiopathic Pulmonary Fibrosis,Fibrocystic Pulmonary Dysplasia,Fibrosing Alveolitis, Cryptogenic,Idiopathic Fibrosing Alveolitis, Chronic Form,Idiopathic Pulmonary Fibrosis, Familial,Interstitial Pneumonitis, Usual,Pulmonary Fibrosis, Idiopathic,Usual Interstitial Pneumonia,Cryptogenic Fibrosing Alveolitides,Dysplasia, Fibrocystic Pulmonary,Fibrocystic Pulmonary Dysplasias,Fibrosing Alveolitides, Cryptogenic,Idiopathic Pulmonary Fibroses,Interstitial Pneumonia, Usual,Pneumonitides, Usual Interstitial,Pneumonitis, Usual Interstitial,Pulmonary Dysplasia, Fibrocystic,Pulmonary Fibroses, Idiopathic,Usual Interstitial Pneumonias,Usual Interstitial Pneumonitides,Usual Interstitial Pneumonitis

Related Publications

Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
January 1998, Roczniki Akademii Medycznej w Bialymstoku (1995),
Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
March 2020, International journal of molecular sciences,
Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
January 1996, Folia histochemica et cytobiologica,
Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
January 2022, Frontiers in immunology,
Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
July 2022, Journal of cellular physiology,
Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
October 2008, Cancer letters,
Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
September 2006, Biochemical and biophysical research communications,
Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
November 2018, Digestive diseases and sciences,
Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
January 2024, Theranostics,
Huijuan Xiao, and Liang Peng, and Dingyuan Jiang, and Yuan Liu, and Lili Zhu, and Zhen Li, and Jing Geng, and Bingbing Xie, and Xiaoxi Huang, and Jing Wang, and Huaping Dai, and Chen Wang
February 2015, The Journal of clinical investigation,
Copied contents to your clipboard!