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Caspase-1 Enhances TANGO1 Expression to Promote Procollagen Export from the Endoplasmic Reticulum in Systemic Sclerosis Contributing to Fibrosis
Journal article   Open access   Peer reviewed

Caspase-1 Enhances TANGO1 Expression to Promote Procollagen Export from the Endoplasmic Reticulum in Systemic Sclerosis Contributing to Fibrosis

Lianne M Connolly, Caya M McFalls, Isabelle G McMahon, Akash M Bhat and Carol M Artlett
Arthritis & rheumatology (Hoboken, N.J.)
17 Apr 2023
DOI: https://doi.org/10.1002/art.42535
PMID: 37067501
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1002/art.42535View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

TANGO1 (Transport ANd Golgi Organization protein 1) is a protein that regulates the export of procollagen from the endoplasmic reticulum and has a role in the organization of exit sites for general protein export. What regulates the expression of TANGO1, and its role in fibrosis, is poorly understood, and has never been studied in systemic sclerosis (SSc). We undertook these studies to determine the role for TANGO1 in SSc fibrosis. SSc (n=15) and healthy (n=12) primary fibroblast lung cell lines were investigated for the expression of TANGO1. Histological analyses for TANGO1 were performed on lung biopsies (n=12 SSc and n=8 healthy). SSc fibroblasts show increased TANGO1 protein in cultured fibroblasts. TANGO1 colocalizes with α-SMA positive cells in SSc lung tissue and is highly upregulated in the neointima of SSc vessels. TANGO1 expression was dependent on the inflammasome activation of caspase-1. It was also dependent on signaling from the IL-1 and TGF-β receptors. The decrease in TANGO1 downregulated export of larger cargos including collagen, and laminin. Reduced TANGO1 protein had no effect on smaller molecular weight cargoes, however, the secretion of elastin was significantly reduced. TANGO1 is markedly increased in SSc fibroblasts and found elevated in lung tissue in association with α-SMA positive cells. TANGO1 expression is driven by inflammasome-dependent caspase-1 activation and is mediated by IL-1 and TGF-β downstream signaling. These observations suggest that during fibrosis, caspase-1 promotes the upregulation of TANGO1, and the organization of ER exits sites, ultimately contributing to procollagen export and fibrosis.

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Rheumatology
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