Heterozygosity of mitogen-activated protein kinase organizer 1 ameliorates diabetic nephropathy and suppresses epithelial-to-mesenchymal transition-like changes in db/db mice

Loeffler I, Liebisch M, Daniel C, Amann KU, Wolf G (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Nephrology Dialysis Transplantation Oxford University Press (OUP): Policy B

DOI: 10.1093/ndt/gfx202

Abstract

Progressive diabetic nephropathy (DN) is characterized by tubulointerstitial fibrosis that is caused by accumulation of extracellular matrix. Induced by several factors, matrix-producing myofibroblasts may to some extent originate from tubular cells by epithelial-to-mesenchymal transition (EMT). Although previous data document that activation of hypoxia-inducible factor (HIF) signalling can be renoprotective in acute kidney disease, this issue remains controversial in chronic kidney injury. Here, we studied whether DN and EMT-like changes are ameliorated in a mouse model of type 2 diabetes mellitus with increased stability and activity of the HIF.We used db/db mice that were crossed with transgenic mice expressing reduced levels of mitogen-activated protein kinase organizer 1 (MORG1), a scaffold protein interacting with prolyl hydroxylase domain 3 (PHD3), because of deletion of one MORG1 allele.We found significantly reduced nephropathy in diabetic MORG1 +/- heterozygous mice compared with the diabetic wild-types ( db/db XMORG1 +/+ ). Furthermore, we demonstrated that EMT-like changes in the tubulointerstitium of diabetic wild-type MORG1 +/+ mice are present, whereas diabetic mice with reduced expression of MORG1 showed significantly fewer EMT-like changes.These findings reveal that a deletion of one MORG1 allele inhibits the development of DN in db/db mice. The data suggest that the diminished interstitial fibrosis in these mice is a likely consequence of suppressed EMT-like changes.

Authors with CRIS profile

Christoph Daniel Department of Nephropathology Kerstin Ute Amann Department of Nephropathology

Involved external institutions

Universitätsklinikum Jena DE Germany (DE)

How to cite

APA:

Loeffler, I., Liebisch, M., Daniel, C., Amann, K.U., & Wolf, G. (2017). Heterozygosity of mitogen-activated protein kinase organizer 1 ameliorates diabetic nephropathy and suppresses epithelial-to-mesenchymal transition-like changes in db/db mice. Nephrology Dialysis Transplantation. https://doi.org/10.1093/ndt/gfx202

MLA:

Loeffler, Ivonne, et al. "Heterozygosity of mitogen-activated protein kinase organizer 1 ameliorates diabetic nephropathy and suppresses epithelial-to-mesenchymal transition-like changes in db/db mice." Nephrology Dialysis Transplantation (2017).

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