Regenerating islet-derived protein 1 inhibits the activation of islet stellate cells isolated from diabetic mice.
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.
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing, China.
Wei
W
Xu
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing, China.
Wei
W
Li
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing, China.
Ying
Y
Wang
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing, China.
Min
M
Zha
Department of Pharmacology, Medical School of Southeast University, Nanjing, China.
Honghong
H
Yao
Diabetes Research Group, Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Peter M
PM
Jones
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing, China.
Zilin
Z
Sun
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D007124:Immunoenzyme Techniques; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D051847:Lithostathine / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014945:Wound Healing
C484685:Extl3 protein, mouse; D051847:Lithostathine; D012333:RNA, Messenger; C497615:Reg1 protein, mouse; D017351:N-Acetylglucosaminyltransferases
Pathology Section; exostosin-like glycosyltransferase 3; islet fibrosis; islet stellate cells; regenerating islet-derived protein 1