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Updated: Apr 28, 2026
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Death associated protein kinase 2 is expressed in cortical interstitial cells of the mouse kidney
Justin A Guay, Don M Wojchowski1, Jing Fang
1Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA. Wojchd@mmc.org.
Background:
DAPK2 is a pro-apoptotic protein kinase that associates with TGFβ receptors. The homolog DAPK1 has been shown to mediate apoptosis in kidney injury. Expression databases indicate that DAPK2 is expressed in the kidney, and in this work we investigate the localization of renal DAPK2 expression and its role in the kidney.
Results:
Immunostaining demonstrates DAPK2 expression in interstitial cells of the renal cortex including PDGFRβ-positive pericytes and the CD73-positive erythropoietin-expressing fibroblast population. Tubulointerstitial fibrosis in experimental CKD arises directly from resident interstitial cells, and we therefore evaluated the expression of DAPK2 in the expanded interstitium of mice with kidney disease induced by chronic cisplatin administration. Expanded renal interstitium in these animals was negative for DAPK2 expression, but healthy areas of the kidney in which the tubular interstitium had not expanded expressed DAPK2 at levels similar to the uninjured control. Dapk2 null mice were generated to evaluate if DAPK2 is required for formation of the kidney, or its maintenance in the adult. Kidneys of Dapk2 null mice did not show overt malformations or age-related degeneration, but did show a slight increase in the number of interstitial fibroblasts. Differences were seen between Dapk2 null mice and wild type controls in the response to tubulointerstitial fibrosis caused by chronic cisplatin administration. Although mutant and wild type mice displayed comparable levels of alpha smooth muscle actin, interstitial proliferation and SMAD2 signaling, Dapk2 null mice showed reduced interstitial collagen accumulation.
Conclusions:
In the kidney, DAPK2 is strongly and specifically expressed in interstitial cells of the cortex, providing a useful marker for this important cell population. Dapk2 null mice are phenotypically normal under steady state conditions, but display some resistance to extracellular matrix deposition in experimental renal fibrosis indicating that DAPK2 plays a profibrotic role in kidney injury.
Insights
Death-associated protein kinase 2 (DAPK2) is found in kidney interstitial cells. DAPK2 null mice show reduced fibrosis, indicating DAPK2 promotes kidney fibrosis.
Area of Science:
- Cell Biology
- Renal Physiology
- Molecular Medicine
Background:
- DAPK2 is a pro-apoptotic protein kinase.
- DAPK2 associates with TGFβ receptors.
- DAPK2 is expressed in the kidney.
Purpose of the Study:
- Investigate renal DAPK2 expression localization.
- Determine the role of DAPK2 in kidney injury and fibrosis.
Main Methods:
- Immunostaining of renal DAPK2 expression.
- Generation and analysis of Dapk2 null mice.
- Induction of experimental chronic kidney disease (CKD) using cisplatin.
Main Results:
- DAPK2 is expressed in renal cortical interstitial cells, including pericytes and fibroblasts.
- DAPK2 expression is reduced in expanded interstitium during CKD.
- Dapk2 null mice show normal kidney development but increased interstitial fibroblasts.
- Dapk2 null mice exhibit reduced interstitial collagen accumulation in experimental renal fibrosis.
Conclusions:
- DAPK2 is a specific marker for renal interstitial cells.
- DAPK2 plays a profibrotic role in kidney injury.
- DAPK2 deficiency confers resistance to extracellular matrix deposition in renal fibrosis.
