Oncotarget

Research Papers: Pathology:

Regenerating islet-derived protein 1 inhibits the activation of islet stellate cells isolated from diabetic mice

Wei Xu, Wei Li, Ying Wang, Min Zha, Honghong Yao, Peter M. Jones and Zilin Sun _

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Oncotarget. 2015; 6:37054-37065. https://doi.org/10.18632/oncotarget.6163

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Abstract

Wei Xu1, Wei Li1, Ying Wang1, Min Zha1, Honghong Yao2, Peter M. Jones3 and Zilin Sun1

1 Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing, China

2 Department of Pharmacology, Medical School of Southeast University, Nanjing, China

3 Diabetes Research Group, Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK

Correspondence to:

Zilin Sun, email:

Peter M. Jones, email:

Keywords: regenerating islet-derived protein 1, exostosin-like glycosyltransferase 3, islet stellate cells, islet fibrosis, Pathology Section

Received: July 06, 2015 Accepted: October 04, 2015 Published: October 19, 2015

Abstract

Emerging evidence indicates that the islet fibrosis is attributable to activation of islet stellate cells (ISCs). In the present study, we compared the differences in biological activity of ISCs isolated from diabetic db/db and non-diabetic db/m mice, and the effects of the regenerating islet-derived protein 1 (Reg1) on ISC function. We showed that ISCs isolated from db/db mice were activated more rapidly than those from db/m mice during culture. Both Reg1 and its putative receptor exostosin-like glycosyltransferase 3 (EXTL3) were highly expressed by diabetic ISCs. Treatment with Reg1 inhibited migration, viability, and synthesis and secretion of Type I Collagen(Col-I), Type III Collagen(Col-III) and Fibronectin(FN) by diabetic ISCs, and this was associated with deactivation of the PI3K/Akt, MAPK/Erk1/2 signaling pathway in an EXTL3-dependent manner. In conclusion, our observations (i) confirmed the presence of fibrogenic stellate cells within pancreatic islets, which are prone to be activated in Type 2 diabetes, and (ii) revealed a potential role for Reg1 in preventing ISC activation.


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