Bogdani Marika, Korpos Eva, Simeonovic Charmaine J, Parish Christopher R, Sorokin Lydia, Wight Thomas N
Matrix Biology Program, Benaroya Research Institute, 1201 Ninth Avenue, Seattle, WA, 98101, USA,
Curr Diab Rep. 2014 Dec;14(12):552. doi: 10.1007/s11892-014-0552-7.
Type 1 diabetes (T1D) results from progressive immune cell-mediated destruction of pancreatic β cells. As immune cells migrate into the islets, they pass through the extracellular matrix (ECM). This ECM is composed of different macromolecules localized to different compartments within and surrounding islets; however, the involvement of this ECM in the development of human T1D is not well understood. Here, we summarize our recent findings from human and mouse studies illustrating how specific components of the islet ECM that constitute basement membranes and interstitial matrix of the islets, and surprisingly, the intracellular composition of islet β cells themselves, are significantly altered during the pathogenesis of T1D. Our focus is on the ECM molecules laminins, collagens, heparan sulfate/heparan sulfate proteoglycans, and hyaluronan, as well as on the enzymes that degrade these ECM components. We propose that islet and lymphoid tissue ECM composition and organization are critical to promoting immune cell activation, islet invasion, and destruction of islet β cells in T1D.
1型糖尿病（T1D）是由免疫细胞介导的胰腺β细胞进行性破坏所致。当免疫细胞迁移到胰岛时，它们会穿过细胞外基质（ECM）。这种ECM由定位于胰岛内部和周围不同隔室的不同大分子组成；然而，这种ECM在人类T1D发生发展中的作用尚未得到充分了解。在这里，我们总结了我们最近在人类和小鼠研究中的发现，这些发现说明了构成胰岛基底膜和间质基质的胰岛ECM的特定成分，以及令人惊讶的是，胰岛β细胞本身的细胞内成分，在T1D发病机制中是如何显著改变的。我们关注的是ECM分子层粘连蛋白、胶原蛋白、硫酸乙酰肝素/硫酸乙酰肝素蛋白聚糖和透明质酸，以及降解这些ECM成分的酶。我们认为，胰岛和淋巴组织的ECM组成和组织对于促进T1D中免疫细胞激活、胰岛侵袭和胰岛β细胞破坏至关重要。
