Department of Basic Medical Sciences, Neurosciences and Sensory Organs (SMBNOS), Section of Human Anatomy and Histology, University of Bari "Aldo Moro", I-70124 Bari, Italy.
Int J Mol Sci. 2021 Mar 21;22(6):3203. 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.
人们对转化生长因子-β（TGF-β）的作用机制进行了大量研究，因为它是包括癌症、纤维化和自身免疫性疾病在内的多种人类疾病的核心介质。TGF-β 通过细胞膜结合的丝氨酸/苏氨酸激酶受体发挥作用，这些受体通过下游信号分子 SMAD 传递信号，SMAD 与各种共激活因子和共抑制因子协同调控靶基因的转录。到目前为止，原发性干燥综合征（pSS）的治疗策略一直集中在炎症上，但最近已经证明 TGF-β/SMADs 信号通路在 pSS 唾液腺（SG）中作为上皮间质转化（EMT）激活的介质参与其中。尽管 EMT 似乎导致 pSS SG 纤维化，但 TGF-β 家族成员对 pSS SG 的功能有多种影响。基于这些前提，本文综述了最近在揭示 TGF-β 在 pSS 中的多方面功能的分子基础方面的进展，这些功能是由 SMAD 的协调决定的，并描述了 TGF-β/SMADs 作为 pSS 的疾病标志物和/或治疗靶点的价值。
