Zhu Yingying, Yang Mei, Xu Wanli, Zhang Yun, Pan Linlin, Wang Lina, Wang Furong, Lu Yanting
Traditional Chinese Medical college, Shandong University of Traditional Chinese Medicine, Jinan, 250300, Shandong, China.
Endocrine. 2024 Mar;83(3):537-547. doi: 10.1007/s12020-023-03592-4. Epub 2023 Nov 24.
The extracellular matrix (ECM) provides an appropriate microenvironment for many kinds of cells, including pancreatic cells. Collagens are the most abundant components of the ECM. Type I, IV, V and VI collagen has been detected in pancreatic islets, and each type plays important role in the proliferation, survival, function and differentiation of pancreatic cells. In some cases, collagens show behaviours similar to those of growth factors and regulate the biological behaviour of β cells by binding with certain growth factors, including IGFs, EGFs and FGFs. The transcriptional coactivator YAP/TAZ has been widely recognised as a mechanosensor that senses changes in the physical characteristics of the ECM and inhibition of YAP/TAZ enhances insulin production and secretion. Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterised by the destruction of insulin-producing β cells. The crosstalk between collagens and immune cells plays a key role in the development and differentiation of immune cells. Further, Supplementation with collagens during islet transplantation is a promising strategy for improving the quality of the islets. But, excessive collagen deposition results in pancreatic fibrosis and pancreatic carcinoma. Targeting inhibit Piezo, autophagy or IL-6 may reduce excessive collagen deposition-induced pancreatic fibrosis and pancreatic carcinoma. This review provides insights into the treatment of T1DM to prolong life expectancy and provides the potential targets for treating collagen deposition-induced pancreatic fibrosis and pancreatic carcinoma.
细胞外基质（ECM）为包括胰腺细胞在内的多种细胞提供了适宜的微环境。胶原蛋白是细胞外基质中含量最为丰富的成分。在胰岛中已检测到I型、IV型、V型和VI型胶原蛋白，且每种类型在胰腺细胞的增殖、存活、功能及分化过程中均发挥着重要作用。在某些情况下，胶原蛋白表现出与生长因子类似的行为，并通过与某些生长因子（包括胰岛素样生长因子、表皮生长因子和成纤维细胞生长因子）结合来调节β细胞的生物学行为。转录共激活因子YAP/TAZ已被广泛认为是一种机械传感器，可感知细胞外基质物理特性的变化，抑制YAP/TAZ可增强胰岛素的产生和分泌。1型糖尿病（T1DM）是一种自身免疫性疾病，其特征是产生胰岛素的β细胞遭到破坏。胶原蛋白与免疫细胞之间的相互作用在免疫细胞的发育和分化中起关键作用。此外，在胰岛移植期间补充胶原蛋白是提高胰岛质量的一种有前景的策略。但是，胶原蛋白过度沉积会导致胰腺纤维化和胰腺癌。靶向抑制Piezo、自噬或白细胞介素-6可能会减少过度胶原蛋白沉积引起的胰腺纤维化和胰腺癌。本综述为延长1型糖尿病患者的预期寿命提供了治疗思路，并为治疗胶原蛋白沉积引起的胰腺纤维化和胰腺癌提供了潜在靶点。
