Integrative Analysis Reveals Common and Unique Roles of Tetraspanins in Fibrosis and Emphysema

Tripathi, Lokesh P. and Itoh, Mari N. and Takeda, Yoshito and Tsujino, Kazuyuki and Kondo, Yasushi and Kumanogoh, Atsushi and Mizuguchi, Kenji (2020) Integrative Analysis Reveals Common and Unique Roles of Tetraspanins in Fibrosis and Emphysema. Frontiers in Genetics, 11. ISSN 1664-8021

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Abstract

While both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are multifactorial disorders characterized by distinct clinical and pathological features, their commonalities and differences have not been fully elucidated. We sought to investigate the preventive roles of tetraspanins Cd151 and Cd9 -that are involved in diverse cellular processes in lung pathophysiology- in pulmonary fibrosis and emphysema, respectively, and to obtain a deeper understanding of their underlying molecular mechanisms toward facilitating improved therapeutic outcomes. Using an integrative approach, we examined the transcriptomic changes in the lungs of Cd151- and Cd9-deficient mice using functional-enrichment-analysis, pathway-perturbation-analysis and protein-protein-interaction (PPI) network analysis. Circadian-rhythm, extracellular-matrix (ECM), cell-adhesion and inflammatory responses and associated factors were prominently influenced by Cd151-deletion. Conversely, cellular-junctions, focal-adhesion, vascular-remodeling, and TNF-signaling were deeply impacted by Cd9-deletion. We also highlighted a “common core” of factors and signaling cascades that underlie the functions of both Cd151 and Cd9 in lung pathology. Circadian dysregulation following Cd151-deletion seemingly facilitated progressive fibrotic lung phenotype. Conversely, TGF-β signaling attenuation and TNF-signaling activation emerged as potentially novel functionaries of Cd9-deletion-induced emphysema. Our findings offer promising avenues for developing novel therapeutic treatments for pulmonary fibrosis and emphysema.

Item Type: Article
Subjects: Grantha Library > Medical Science
Depositing User: Unnamed user with email support@granthalibrary.com
Date Deposited: 27 Jan 2023 08:05
Last Modified: 22 May 2024 09:27
URI: http://asian.universityeprint.com/id/eprint/92

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