Inhibition of gelatinase B (matrix metalloprotease-9) activity reduces cellular inflammation and restores function of transplanted pancreatic islets.

Diabetes
Neelam LingwalThomas Linn

Abstract

Islet transplantation provides an approach to compensate for loss of insulin-producing cells in patients with type 1 diabetes. However, the intraportal route of transplantation is associated with instant inflammatory reactions to the graft and subsequent islet destruction as well. Although matrix metalloprotease (MMP)-2 and -9 are involved in both remodeling of extracellular matrix and leukocyte migration, their influence on the outcome of islet transplantation has not been characterized. We observed comparable MMP-2 mRNA expressions in control and transplanted groups of mice, whereas MMP-9 mRNA and protein expression levels increased after islet transplantation. Immunostaining for CD11b (Mac-1)-expressing leukocytes (macrophage, neutrophils) and Ly6G (neutrophils) revealed substantially reduced inflammatory cell migration into islet-transplanted liver in MMP-9 knockout recipients. Moreover, gelatinase inhibition resulted in a significant increase in the insulin content of transplanted pancreatic islets and reduced macrophage and neutrophil influx compared with the control group. These results indicate that the increase of MMP-9 expression and activity after islet transplantation is directly related to enhanced leukocyte migrat...Continue Reading

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Citations

Apr 4, 2013·Critical Reviews in Biochemistry and Molecular Biology·Jennifer VandoorenGhislain Opdenakker
Feb 11, 2015·The American Journal of Pathology·Gustaf ChristofferssonMia Phillipson
Oct 26, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Chunguang ChenThomas Linn
May 31, 2020·Redox Biology·Eva-Maria HanschmannThomas Linn

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Datasets Mentioned

BETA
GM6001

Methods Mentioned

BETA
PCR
protein assay
FCS
enzyme-linked immunosorbent assay
fluorescence-activated cell sorter

Software Mentioned

Leica
Cell Quest

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