From the Departments of *Surgery and †Paediatrics, Faculty of Medicine, ‡Department of Experimental Therapeutics, Faculty of Pharmaceutical Sciences, University of British Columbia; and §British Columbia Cancer Agency; and ∥Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Pancreas. 2014 Jan;43(1):128-34. doi: 10.1097/MPA.0b013e31829695d2.
B7-H4 is a negative coregulatory molecule known to be involved in immune response. We study here B7-H4 expression and its possible role in diabetes and cancer development.
Formalin-fixed, paraffin-processed pancreas samples from patients with type 1 diabetes (T1D), insulinoma, pancreatic ductal adenocarcinoma (PDAC), and normal organ donors were studied by bright-field and multifluorescence immunohistochemistry to examine B7-H4 expression and its colocalization with islet endocrine hormones. Quantitative RT-PCR and Western blot assay were used to examine B7-H4 mRNA and protein expression in the islet and exocrine tissues from normal donors and pancreatic cancer cell lines.
B7-H4 protein expression in islet β cells is decreased in T1D and PDAC, but increased in insulinoma patients when compared to normal controls; the changes in B7-H4 expression are concomitant with insulin expression on the islet β cells. The insulin/B7-H4 colocalization on the β cells, expressed in colocalization coefficient Pearson r, is also changed in these islets.
Our observation of altered B7-H4 expression, concomitant with insulin expression, in the pancreatic islets of T1D, PDAC, and insulinoma patients when compared to normal controls suggests that B7-H4 pathway might play an important role in maintenance of β-cell function, but its exact role remains to be explored.
B7-H4 是一种负性共刺激分子，已知其参与免疫反应。我们在此研究 B7-H4 的表达及其在糖尿病和癌症发展中的可能作用。
通过明场和多荧光免疫组织化学研究来自 1 型糖尿病 (T1D)、胰岛素瘤、胰腺导管腺癌 (PDAC) 和正常器官供体的福尔马林固定、石蜡处理的胰腺样本，以检查 B7-H4 的表达及其与胰岛内分泌激素的共定位。使用定量 RT-PCR 和 Western blot 检测来自正常供体和胰腺癌细胞系的胰岛和外分泌组织中的 B7-H4 mRNA 和蛋白表达。
与正常对照组相比，T1D 和 PDAC 患者胰岛β细胞中的 B7-H4 蛋白表达降低，但胰岛素瘤患者增加；B7-H4 表达的变化与胰岛β细胞上的胰岛素表达同时发生。β细胞上胰岛素/B7-H4 的共定位（用 Pearson r 表示的共定位系数）也在这些胰岛中发生改变。
与正常对照组相比，我们观察到 T1D、PDAC 和胰岛素瘤患者的胰腺胰岛中 B7-H4 的表达发生改变，与胰岛素表达同时发生，这表明 B7-H4 途径可能在维持β细胞功能方面发挥重要作用，但确切作用仍有待探索。
