New research from Stony Brook Medicine suggests a novel approach to combat diabetic kidney disease (DKD) by targeting cellular signaling between two types of kidney cells. The study, led by Dr. Sandeep K. Mallipattu and Dr. Nehaben A. Gujarati, was published in Nature Communications.
The researchers focused on the interaction between podocyte and proximal tubule cells in the kidneys, aiming to induce a human KLF6 transcription factor within these processes. This approach may help prevent or slow down DKD progression, which is currently the leading cause of chronic kidney disease worldwide.
Drs. Mallipattu and Gujarati used a multi-omics strategy to demonstrate that inducing KLF6 can attenuate podocyte loss and proximal tubule dysfunction, ultimately reducing interstitial fibrosis in later stages of the disease.
Podocytes are crucial for regulating glomerular function, while proximal tubule cells reabsorb water, glucose, and proteins from the filtrate. Both cell types are essential in preventing DKD progression.
In their model, KLF6 triggers Apolipoprotein J secretion from podocytes to activate calcium/calmodulin-dependent protein kinase 1D (CaMK1D) in proximal tubule cells, thereby preventing mitochondrial injury associated with DKD.
“This cell-to-cell communication through this signaling mechanism in the kidney might serve as a protective mechanism in the early stages of DKD,” said Dr. Mallipattu.
The study involved murine models alongside human cells and tissue samples from patients with varying stages of DKD.
“In combination, findings from these studies highlight that targeting podocyte-proximal tubule signaling by enhancing Apolipoprotein J-CaMK1D could prove to be a therapeutic strategy in slowing down or perhaps even preventing DKD,” added Dr. Mallipattu.
Future research will explore pharmacological methods to activate this pathway as a preventive measure against DKD for individuals with diabetes.
Funding for this research came partly from the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases and Dialysis Clinic Inc.