How diabetes affects the kidneys

In a recent publication, researchers at Jena University Hospital (JUH) present the findings of their study into why the kidneys are susceptible to damage to varying degrees in the course of type 2 diabetes. The study focuses on the protein MORG1 (MAPK organiser 1/WDR83), which is involved in regulating key cellular signalling processes. The results show that its influence on diabetic kidney disease depends on the stage of the disease and can change as the condition progresses. The lead author, Jonas Till Ihle, a doctoral candidate at the Department of Internal Medicine III, received funding for this work through the "Gender in Focus – Research Talent" grant scheme, part of the "Gender in Focus" project funded by the Federal Ministry of Research, Technology and Space.

Type 2 diabetes causes kidney damage

Diabetic kidney disease is one of the most common and clinically significant complications of type 2 diabetes mellitus. It is associated with a progressive loss of kidney function and is a major cause of chronic kidney damage. As ageing processes further influence the progression of the disease, a deeper understanding of the underlying molecular changes is of great importance.

For the study, the research team used an established mouse model of type 2 diabetes. Male and female mice in both early and later stages of the disease were analysed, with non-diabetic mice serving as a control group. The focus was on reduced MORG1 expression resulting from a heterozygous deletion (the absence of a gene segment in one of two copies of the gene) of the underlying gene. Both kidney function and changes at the molecular level were investigated. Among other things, the researchers examined scarring of the kidney tissue, protein in the urine, specific biological regulatory mechanisms within the cells, and changes in gene activity in the outer layer of the kidney.

Gender differences are relevant

The results suggest that reduced MORG1 expression in the early stages of the disease is associated with fewer signs of kidney damage. Both reduced scarring of the kidney tissue and lower urinary albumin excretion – which is considered an important marker of impaired kidney function – were observed. In later stages, however, this protective effect was significantly less pronounced. The data suggest that MORG1 is involved in the dynamic changes that characterise the progression of the disease.

Furthermore, the study provides evidence of biological sex differences. For instance, HIF-1α expression (a substance activated in the absence of oxygen) remained comparatively more preserved in female animals with reduced MORG1 expression in later stages of the disease than in other groups. Differences were also observed, depending on genotype and stage of the disease, in the signalling pathways through which cells transmit information and regulate key processes such as growth, metabolism and responses to stress.

The study, published in the International Journal of Molecular Sciences, thus contributes to a more nuanced understanding of diabetic kidney disease. It highlights that the molecular processes contributing to kidney damage in type 2 diabetes do not remain constant over the course of the disease. This provides important starting points for further research into treatment strategies tailored to the stage of the disease and specific to gender.