Ling Gao, Jia-Shuang Lai, Han Chen, Li-Xia Qian, Wan-Jin Hong, Liang-Cheng Li
{"title":"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。","authors":"Ling Gao, Jia-Shuang Lai, Han Chen, Li-Xia Qian, Wan-Jin Hong, Liang-Cheng Li","doi":"10.4239/wjd.v16.i6.102727","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 6","pages":"102727"},"PeriodicalIF":4.2000,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179872/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mechanism of trypsin-mediated differentiation of pancreatic progenitor cells into functional islet-like clusters.\",\"authors\":\"Ling Gao, Jia-Shuang Lai, Han Chen, Li-Xia Qian, Wan-Jin Hong, Liang-Cheng Li\",\"doi\":\"10.4239/wjd.v16.i6.102727\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":48607,\"journal\":{\"name\":\"World Journal of Diabetes\",\"volume\":\"16 6\",\"pages\":\"102727\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-06-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179872/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Diabetes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4239/wjd.v16.i6.102727\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4239/wjd.v16.i6.102727","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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.
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.