期刊
CURRENT DIABETES REPORTS
卷 14, 期 12, 页码 552-U14出版社
CURRENT MEDICINE GROUP
DOI: 10.1007/s11892-014-0552-7
关键词
Extracellular matrix; Hyaluronan; Hyaladherins; Laminin; Heparan sulfate; Cathepsins; Heparanase; Islet; Islet infiltration; Diabetes; Immune regulation
资金
- European Foundation for the Study of Diabetes/Juvenile Diabetes Research Foundation (JDRF)/Novo Nordisk A/S [BD21070]
- JDRF [1-2005-903]
- German Research Foundation Collaborative Research Center (CRC) [1009, SO285/9-1]
- National Health and Medical Research Council of Australia (NH & MRC)/JDRF Special Program Grant in Type 1 Diabetes [418138]
- NHMRC [1043284]
- Roche Organ Transplantation Research Foundation (ROTRF)/JDRF [477554991]
- JDRF nPOD grant [25-2010-648]
- NIH/NIAID [U01 AI101990, U01 AI101984]
- Network for Pancreatic Organ Donors with Diabetes (nPOD), a collaborative type 1 diabetes research project - JDRF
Type 1 diabetes (T1D) results from progressive immune cell-mediated destruction of pancreatic beta cells. As immune cells migrate into the islets, they pass through the extracellular matrix (ECM). This ECM is composed of different macromolecules localized to different compartments within and surrounding islets; however, the involvement of this ECM in the development of human T1D is not well understood. Here, we summarize our recent findings from human and mouse studies illustrating how specific components of the islet ECM that constitute basement membranes and interstitial matrix of the islets, and surprisingly, the intracellular composition of islet beta cells themselves, are significantly altered during the pathogenesis of T1D. Our focus is on the ECM molecules laminins, collagens, heparan sulfate/heparan sulfate proteoglycans, and hyaluronan, as well as on the enzymes that degrade these ECM components. We propose that islet and lymphoid tissue ECM composition and organization are critical to promoting immune cell activation, islet invasion, and destruction of islet Beta cells in T1D.
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