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Altered Expression of EMT-Related Factors Snail, Wnt4, and Notch2 in the Short-Term Streptozotocin-Induced Diabetic
Matea Dragun Jurić1, Anita Racetin2, Natalija Filipović2
1Intensive Care Unit of the Department of Internal Medicine, University Hospital in Split, 21000 Split, Croatia.
Abstract:
Background: The aim of this study was to determine the expression of epithelial to mesenchymal transition (EMT)-related transcription factors Snail, Wnt4, and Notch2 with key roles in renal fibrosis, in different renal areas of diabetic rats: glomeruli (G), proximal and distal convoluted tubules (PCT; DCT). Methods: Male Sprague Dawley rats were instilled with 55 mg/kg streptozotocin (diabetes mellitus type I model, DM group) or citrate buffer (control group). Kidney samples were collected 2 weeks and 2 months after DM induction and processed for immunohistochemistry. Results: Diabetic animals showed higher Wnt4 kidney expression both 2 weeks and 2 months post-DM induction, while Snail expression significantly increased only 2 weeks after DM initiation (p < 0.0001). We determined significantly higher expression of examined EMT-related genes in different kidney regions in diabetic animals compared with controls. The most substantial differences were observed in tubular epithelial cells in the period of 2 weeks after induction, with higher Snail and Wnt4 expression in PCT and increased Snail and Notch2 expression in DCT of diabetic animals (p < 0.0001; p < 0.001). Conclusion: The obtained results point to the EMT-related factors Snail, Wnt4, and Notch2 as a potential contributor to diabetic nephropathy development and progression. Changes in their expression, especially in PCT and DCT, could serve as diagnostic biomarkers for the early stages of DM and might be a promising novel therapeutic target in this condition.
Insights
Diabetic nephropathy is linked to increased expression of epithelial to mesenchymal transition (EMT) factors Snail, Wnt4, and Notch2, particularly in kidney tubules. These factors may serve as early diagnostic biomarkers and therapeutic targets.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Diabetic nephropathy is a leading cause of kidney failure.
- Epithelial to mesenchymal transition (EMT) plays a critical role in renal fibrosis.
- EMT-related transcription factors like Snail, Wnt4, and Notch2 are implicated in kidney disease progression.
Purpose of the Study:
- To investigate the expression of EMT-related transcription factors (Snail, Wnt4, Notch2) in different renal regions of diabetic rats.
- To correlate changes in these factors with the development and progression of diabetic nephropathy.
Main Methods:
- A type 1 diabetes mellitus (DM) model was established in male Sprague Dawley rats using streptozotocin.
- Kidney samples were analyzed via immunohistochemistry at 2 weeks and 2 months post-DM induction.
- Expression levels of Snail, Wnt4, and Notch2 were quantified in glomeruli (G), proximal convoluted tubules (PCT), and distal convoluted tubules (DCT).
Main Results:
- Diabetic rats exhibited significantly higher Wnt4 expression in the kidneys at both time points.
- Snail expression was significantly elevated at 2 weeks post-DM induction.
- The most pronounced increases in Snail, Wnt4, and Notch2 were observed in PCT and DCT cells of diabetic animals, especially at the 2-week mark.
Conclusions:
- EMT-related factors Snail, Wnt4, and Notch2 are potential contributors to diabetic nephropathy.
- Altered expression of these factors in renal tubules may serve as early diagnostic biomarkers for diabetes.
- These factors represent promising novel therapeutic targets for managing diabetic nephropathy.
