SMADS-Mediate Molecular Mechanisms in Sjögren's Syndrome

• Published in: International journal of molecular sciences Vol. 22; no. 6; p. 3203
• Main Authors: Sisto, Margherita, Ribatti, Domenico, Lisi, Sabrina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 21.03.2021; MDPI AG
• Subjects: Animals; Biomarkers; Cytokines - metabolism; Disease Susceptibility; Epithelial-Mesenchymal Transition; Fibrosis; Gene Expression Regulation; Humans; inflammation; Inflammation Mediators - metabolism; Phosphorylation; Protein Binding; Review; Signal Transduction; Sjogren's Syndrome - etiology; Sjogren's Syndrome - metabolism; Sjogren's Syndrome - pathology; Sjögren’s syndrome; SMAD; Smad Proteins - genetics; Smad Proteins - metabolism; TGF-β; Transforming Growth Factor beta - metabolism; Sjögren’s syndrome; TGF-β; epithelial-mesenchymal transition; fibrosis; SMAD; inflammation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22063203

There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjögren's syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS salivary glands (SGs) as mediator of the epithelial-mesenchymal transition (EMT) activation. Although EMT seems to cause pSS SG fibrosis, TGF-β family members have ambiguous effects on the function of pSS SGs. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.