PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis.

Autor: Sun B; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA., Tomita B; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA., Salinger A; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Tilvawala RR; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Li L; Department of Anatomy and Cell Biology and Faculty of Dentistry, McGill University, Montreal, QC H3A 0C7, Canada., Hakami H; Department of Anatomy and Cell Biology and Faculty of Dentistry, McGill University, Montreal, QC H3A 0C7, Canada., Liu T; Harvard Medical School, Boston, MA 02115, USA; Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA., Tsoyi K; Pulmonary, Critical Care and Sleep Medicine Section, Baylor College of Medicine, Houston, TX 77030, USA., Rosas IO; Pulmonary, Critical Care and Sleep Medicine Section, Baylor College of Medicine, Houston, TX 77030, USA., Reinhardt DP; Department of Anatomy and Cell Biology and Faculty of Dentistry, McGill University, Montreal, QC H3A 0C7, Canada., Thompson PR; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Ho IC; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: iho@bwh.harvard.edu.
Jazyk: angličtina
Zdroj: Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2021 Aug; Vol. 102, pp. 70-84. Date of Electronic Publication: 2021 Jul 15.
DOI: 10.1016/j.matbio.2021.07.001
Abstrakt: The formation of elastic fibers is active only in the perinatal period. How elastogenesis is developmentally regulated is not fully understood. Citrullination is a unique form of post-translational modification catalyzed by peptidylarginine deiminases (PADs), including PAD1-4. Its physiological role is largely unknown. By using an unbiased proteomic approach of lung tissues, we discovered that FBLN5 and LTBP4, two key elastogenic proteins, were temporally modified in mouse and human lungs. We further demonstrated that PAD2 citrullinated FBLN5 preferentially in young lungs compared to adult lungs. Genetic ablation of PAD2 resulted in attenuated elastogenesis in vitro and age-dependent emphysema in vivo. Mechanistically, citrullination protected FBLN5 from proteolysis and subsequent inactivation of its elastogenic activity. Furthermore, citrullinated but not native FBLN5 partially rescued in vitro elastogenesis in the absence of PAD activity. Our data uncover a novel function of citrullination, namely promoting elastogenesis, and provide additional insights to how elastogenesis is regulated.
Competing Interests: Conflict of interest The authors declared that no conflict of interest exists.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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