Clinic for Internal Medicine III, Research lab Nephrology

Research topic(s)

MORG1, also known as WDR83, is a scaffold protein in the HIF and Erk signaling pathway. We demonstrated that reduction of MORG1 expression is protective against hypoxia- and diabetes-induced renal injury. Mechanisms such as preconditioning, lipotoxicity, or tubulointerstitial fibrosis play a role. The pathological changes in the aging kidney are similar to those in diabetic or other fibrotic kidney diseases. Thus, in the aging kidney, changes in lipid metabolism have also been described as causative for the damage. The aim of this project is to investigate in a mouse model whether a reduction of MORG1 in aging also has a renoprotective effect or whether possibly a long-term activation of HIF by MORG1 reduction has a more pathological effect on the kidney. It should also be clarified whether MORG1 here, in contrast to diabetic nephropathy in type 1 or type 2 diabetes mellitus, interferes with lipid metabolism at a different site and whether any influence of MORG1 in the aging kidney is more likely due to its function in the HIF or MAPK pathway (or both?).

Methods

• Aging model in mice: Wildtype and heterozygous MORG1 knockout mice of different age (young, middle, old)
• Analysis of renal function and morphological changes in the kidneys: ELISA with urine, histology and immunhistochemistry (IHC) on kidney sections
• Analysis of expression of profibrotic genes and proteins of lipid metabolism: mRNA (qPCR) and protein (IHC/IF and Western blot)

Selected Publications

Jankowski E, Wulf S, Ziller N, Wolf G, Loeffler I. (2021)  MORG1-A negative modulator of renal lipid metabolism in murine diabetes.External link Biomedicines, 10(1):30

Loeffler I, Liebisch M, Daniel C, Amann K, 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.External link Nephrol Dial Transplant, 32(12):2017-2034

Loeffler I, Wolf G. (2015) Morg1 heterozygous deficiency ameliorates hypoxia-induced acute renal injury.External link Am J Physiol Renal Physiol, 308(6):F511-21

Hammerschmidt E, Loeffler I, Wolf G. (2009) Morg1 heterozygous mice are protected from acute renal ischemia-reperfusion injury. External linkAm J Physiol Renal Physiol, 297(5):F1273-1287

Hopfer U, Hopfer H, Jablonski K, Stahl R, Wolf G. (2006) The novel WD-repeat protein Morg1 acts as a molecular scaffold for hypoxia-inducible factor prolyl hydroxylase 3 (PHD3)External link. J Biol Chem, 281(13):8645-8655

Links

Learn moreExternal link

ResearchGate Profile of Gunter WolfExternal link

ResearchGate Profile of Ivonne LoefflerExternal link