The role and mechanism of CRISPLD2 in skin fibrosis of systemic sclerosis.

Abstract

SSc is an autoimmune connective tissue disease involving multiple organs. The most common clinical symptom of SSc is progressive fibrosis of the skin, and the pathologically manifestations of skin were activation and proliferation of fibroblasts and continuous proliferation of extracellular matrix. TGF-β can promote the proliferation and activation of fibroblasts, causing excessive deposition of collagen and structural proteins. Therefore, exploring the specific mechanism of TGF-β-related pathway on fibrosis is of great significance for improving skin fibrosis in SSc. Genes related to TGF-β pathway were screened through bioinformatics analysis, and SSc phenotypes were verified in vivo and in vitro. The relevant molecular mechanisms were preliminarily discussed in combination with transcriptome sequencing. Human cysteine-rich secreted protein LCCL domain protein 2 (CRISPLD2) was found increased reactivity in TGF-β-induced fibroblasts, and the expression of ACTA2 (ɑ-SMA) decreased significantly in TGF-β-mediated fibroblasts with up-regulation of CRISPLD2. CRISPLD2 was found to have increased reactivity in TGF-β-induced fibroblasts, and we further confirmed that CRISPLD2 can participate in TGF-β-induced fibroblast fibrosis from multiple perspectives and levels in negative feedback regulation, and investigated the mechanism of CRISPLD2 in fibrosis.