Hull Rebecca L, Bogdani Marika, Nagy Nadine, Johnson Pamela Y, Wight Thomas N
Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and University of Washington (RLH)
Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington (MB, NN, PYJ, TNW)
J Histochem Cytochem. 2015 Aug;63(8):592-603. doi: 10.1369/0022155415576542.
Hyaluronan (HA) is an extracellular matrix (ECM) component that is present in mouse and human islet ECM. HA is localized in peri-islet and intra-islet regions adjacent to microvessels. HA normally exists in a high molecular weight form, which is anti-inflammatory. However, under inflammatory conditions, HA is degraded into fragments that are proinflammatory. HA accumulates in islets of human subjects with recent onset type 1 diabetes (T1D), and is associated with myeloid and lymphocytic islet infiltration, suggesting a possible role for HA in insulitis. A similar accumulation of HA, in amount and location, occurs in non-obese diabetic (NOD) and DORmO mouse models of T1D. Furthermore, HA accumulates in follicular germinal centers and in T-cell areas in lymph nodes and spleen in both human and mouse models of T1D, as compared with control tissues. Whether HA accumulates in islets in type 2 diabetes (T2D) or models thereof has not been previously described. Here we show evidence that HA accumulates in a mouse model of islet amyloid deposition, a well-known component of islet pathology in T2D. In summary, islet HA accumulation is a feature of both T1D and a model of T2D, and may represent a novel inflammatory mediator of islet pathology.
透明质酸（HA）是一种细胞外基质（ECM）成分，存在于小鼠和人类胰岛的ECM中。HA定位于胰岛周围以及与微血管相邻的胰岛内区域。HA通常以高分子量形式存在，具有抗炎作用。然而，在炎症条件下，HA会降解为促炎片段。HA在近期发病的1型糖尿病（T1D）患者的胰岛中积聚，并与髓样和淋巴细胞性胰岛浸润相关，提示HA在胰岛炎中可能发挥作用。在T1D的非肥胖糖尿病（NOD）和DORmO小鼠模型中，HA在数量和位置上有类似的积聚情况。此外，与对照组织相比，在人类和小鼠T1D模型中，HA在滤泡生发中心以及淋巴结和脾脏的T细胞区域积聚。此前尚未描述过HA是否在2型糖尿病（T2D）或其模型的胰岛中积聚。在此我们提供证据表明，HA在胰岛淀粉样变沉积的小鼠模型中积聚，胰岛淀粉样变是T2D胰岛病理学的一个众所周知的组成部分。总之，胰岛HA积聚是T1D和一种T2D模型的共同特征，可能代表胰岛病理学的一种新型炎症介质。
