Expression and function of alphabeta1 integrins in pancretic beta (INS-1) cells.
Expression and function of alphabeta1 integrins in pancretic beta (INS-1) cells.
复制标题
DOI：
10.1007/s12079-008-0030-6
复制
发表时间：
2008-12
影响因子：
4.1
通讯作者：
Wang, Rennian
中科院分区：
文献类型：
--
作者：
Krishnamurthy, Mansa;Li, Jinming;Al-Masri, Maia;Wang, Rennian
整合素-细胞外基质相互作用是β细胞行为的重要决定因素。β1整联蛋白是一种众所周知的β细胞活性调节因子;然而，对其相关的α亚基知之甚少。在本研究中，在大鼠胰岛素瘤细胞系（INS-1）中检测αβ1整合素表达，以确定其在β细胞存活和功能中的作用。鉴定出与β1整合素相关的7个α亚基，包括α1-6和αV。在这些异源二聚体中，α3β1表达最高。测试了α3β1整联蛋白的常见配体，包括纤连蛋白、层粘连蛋白、胶原蛋白I和胶原蛋白IV，以鉴定最适合INS-1细胞增殖和功能的基质。与在纤连蛋白、层粘连蛋白和对照上培养的细胞相比，暴露于胶原蛋白I和IV的细胞表现出粘附、铺展、细胞活力、增殖和FAK磷酸化的显著增加。整合素依赖性附着也对β细胞功能具有有益作用，增加胶原I和IV上的Pdx-1和胰岛素基因和蛋白质表达，同时增加基础胰岛素释放和在高葡萄糖挑战后增强胰岛素分泌。此外，α3β1整联蛋白的功能性阻断降低了细胞在两种胶原上的粘附、铺展和活力，并降低了Pdx-1和胰岛素表达，表明其与胶原基质的相互作用对β细胞存活和功能很重要。这些结果表明，特异性αβ1整联蛋白-ECM相互作用是INS-1 β细胞存活和功能的关键调节因子，并且在设计用于糖尿病治疗的基于细胞的疗法的最佳条件中将是重要的。
Integrin-extracellular matrix interactions are important determinants of beta cell behaviours. The β1 integrin is a well-known regulator of beta cell activities; however, little is known of its associated α subunits. In the present study, αβ1 integrin expression was examined in the rat insulinoma cell line (INS-1) to identify their role in beta cell survival and function. Seven α subunits associated with β1 integrin were identified, including α1-6 and αV. Among these heterodimers, α3β1 was most highly expressed. Common ligands for the α3β1 integrin, including fibronectin, laminin, collagen I and collagen IV were tested to identify the most suitable matrix for INS-1 cell proliferation and function. Cells exposed to collagen I and IV demonstrated significant increases in adhesion, spreading, cell viability, proliferation, and FAK phosphorylation when compared to cells cultured on fibronectin, laminin and controls. Integrin-dependent attachment also had a beneficial effect on beta cell function, increasing Pdx-1 and insulin gene and protein expression on collagens I and IV, in parallel with increased basal insulin release and enhanced insulin secretion upon high glucose challenge. Furthermore, functional blockade of α3β1 integrin decreased cell adhesion, spreading and viability on both collagens and reduced Pdx-1 and insulin expression, indicating that its interactions with collagen matrices are important for beta cell survival and function. These results demonstrate that specific αβ1 integrin-ECM interactions are critical regulators of INS-1 beta cell survival and function and will be important in designing optimal conditions for cell-based therapies for diabetes treatment.
登录
查看更多内容
影响因子：
3.3
作者：
DELWEL, GO;DEMELKER, AA;SONNENBERG, A
通讯作者：
SONNENBERG, A
影响因子：
7.7
作者：
Bosco, D;Meda, P;Rouiller, DG
通讯作者：
Rouiller, DG
影响因子：
3.6
作者：
VANDEIJNEN, JHM;VANSUYLICHEM, PTR;VANSCHILFGAARDE, R
通讯作者：
VANSCHILFGAARDE, R
DOI：
10.1083/jcb.97.3.935
发表时间：
1983-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Montesano R;Mouron P;Amherdt M;Orci L
通讯作者：
Orci L
影响因子：
4.8
作者：
ASFARI, M;JANJIC, D;WOLLHEIM, CB
通讯作者：
WOLLHEIM, CB