胰蛋白酶介导的胰腺祖细胞向功能胰岛样细胞簇分化的机制。

IF 4.2 3区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Ling Gao, Jia-Shuang Lai, Han Chen, Li-Xia Qian, Wan-Jin Hong, Liang-Cheng Li
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引用次数: 0

摘要

背景:胰岛β细胞内源性再生是治疗1型和晚期2型糖尿病的一条途径。胰腺癌细胞系-1 (PANC-1)是人胰岛祖细胞系,胰蛋白酶可诱导其分化为分泌胰岛素的胰岛样聚集体(ILAs)。然而,其潜在机制尚未被探索。目的:探讨胰蛋白酶诱导胰岛祖细胞向胰岛素分泌细胞分化的机制和信号通路。方法:胰蛋白酶诱导PANC-1细胞形成ILAs并向胰岛素分泌细胞分化。集群规则间隔短回文重复(CRISPR)相关蛋白9敲除和小干扰RNA敲除技术用于研究参与该过程的膜蛋白和下游信号通路。结果:胰蛋白酶水解膜受体E-cadherin的胞外结构域诱导PANC-1细胞聚集,刺激E-cadherin募集的酪蛋白激酶-1γ - 3,特异性磷酸化cadherin-catenin复合物中α-catenin的Ser655/Thr658位点,参与PANC-1分化过程,影响分化ILAs的成熟。结论:本研究揭示了胰蛋白酶促进PANC-1细胞向胰岛样细胞分化的机制,为内源性胰岛β细胞再生提供了新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mechanism of trypsin-mediated differentiation of pancreatic progenitor cells into functional islet-like clusters.

Background: Endogenous regeneration of pancreatic islet β-cells is a path to cure both type 1 and advanced type 2 diabetes. Pancreatic cancer cell line-1 (PANC-1), a human pancreatic islet progenitor cell line, can be induced by trypsin to differentiate into insulin-secreting islet-like aggregates (ILAs). However, the underlying mechanism has not been explored.

Aim: To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.

Methods: PANC-1 cells were induced by trypsin to form ILAs and differentiate into insulin-secreting cells. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 knockout and small interfering RNA knockdown techniques were used to investigate membrane proteins and downstream signaling pathways involved in the process.

Results: The extracellular domain of membrane receptor E-cadherin hydrolyzed by trypsin induced the aggregation of PANC-1 cells and stimulated E-cadherin-recruited casein kinase-1γ3, which specifically phosphorylated the Ser655/Thr658 site of α-catenin in the cadherin-catenin complex, participating in the process of PANC-1 differentiation and affecting the maturation of differentiated ILAs.

Conclusion: The current study reveals the mechanism by which trypsin promotes PANC-1 cell differentiation into islet-like cells, providing a novel approach for endogenous islet β-cell regeneration.

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来源期刊
World Journal of Diabetes
World Journal of Diabetes ENDOCRINOLOGY & METABOLISM-
自引率
2.40%
发文量
909
期刊介绍: The WJD is a high-quality, peer reviewed, open-access journal. The primary task of WJD is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of diabetes. In order to promote productive academic communication, the peer review process for the WJD is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJD are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in diabetes. Scope: Diabetes Complications, Experimental Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetes, Gestational, Diabetic Angiopathies, Diabetic Cardiomyopathies, Diabetic Coma, Diabetic Ketoacidosis, Diabetic Nephropathies, Diabetic Neuropathies, Donohue Syndrome, Fetal Macrosomia, and Prediabetic State.
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