Abstract
Systemic sclerosis is a rare chronic heterogenous disease that involves inflammation and vasculopathy, and converges in end-stage development of multisystem tissue fibrosis. The loss of tight spatial distribution and temporal expression of proteins in the extracellular matrix (ECM) leads to progressive organ stiffening, which is a hallmark of fibrotic disease. A group of nonstructural matrix proteins, known as matricellular proteins (MCPs) are implicated in dysregulated processes that drive fibrosis such as ECM remodeling and various cellular behaviors. Accordingly, MCPs have been described in the context of fibrosis in sclerosis (SSc) as predictive disease biomarkers and regulators of ECM synthesis, with promising therapeutic potential. In this present review, an informative summary of major MCPs is presented highlighting their clear correlations to SSc- fibrosis.
Highlights
Systemic sclerosis (SSc) is a rare idiopathic disease that presents as a trifecta of compounding chronic abnormalities driven by autoimmunity, vasculopathy, and systemic tissue fibrosis [1]
The burden of organ fibrosis in SSc is the driving motivation behind a large number of novel research studies, with nearly double the amount of studies published on NCBI PubMed within the last decade (2470 publications listed under the key search terms of “systemic sclerosis” + “fibrosis”) compared to previous years (1484 publications)
RT-PCR analysis of fibroblasts isolated from lesioned skin of dcSSc patients show an upregulation of fibrotic extracellular matrix (ECM) genes COL1A2 and COL3A1, as well as fibrotic matricellular proteins (MCPs) genes Secreted Protein Acidic and Rich in Cysteine (SPARC) and CCN2 when compared to healthy controls [117]
Summary
Systemic sclerosis (SSc) is a rare idiopathic disease that presents as a trifecta of compounding chronic abnormalities driven by autoimmunity, vasculopathy, and systemic tissue fibrosis [1]. SSc carries considerable phenotypic heterogeneity, which leads to the poorly understood complex interplay amongst the dysregulated systems As it affects major internal organ systems, such as the lungs and heart during disease progression, the fibrotic tissue decreases survival probability, and accounts for a large proportion of SSc-related deaths due to organ failure [2]. Canonical Wnt-signaling in myofibroblasts via its ligands Wnt, Wnt-3a, and Wnt-10b have been shown to upregulate expression of ECM encoding genes under ECM restructuring conditions [20,27,28] These pathways along with many others described in the literature empower myofibroblasts to be the driving force in fibrotic pathologies. MCPs have been emerging for their profound effects on myofibroblasts, such as their differentiation, recruitment, collagen synthesis, and apoptotic evasion under fibrotic conditions [19,20,30,31]
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