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Updated: Jul 5, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Apoptosis induced by endoplasmic reticulum stress involved in diabetic kidney disease
Guanghui Liu1, Yingying Sun, Zhenhua Li
1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Abstract:
Endoplasmic reticulum stress has been suggested to play a crucial role in the pathogenesis of diabetic complications. However, whether it is involved in the renal injury of diabetic nephropathy is still not known. We investigated the involvement of ER-associated apoptosis in kidney disease of streptozocin (STZ)-induced diabetic rats. We used albuminuria examination, hematoxylin & eosin (H&E) staining and TUNEL analysis to identify the existence of diabetic nephropathy and enhanced apoptosis. We performed immunohistochemistry, Western blot, and real-time PCR to analyze indicators of ER molecule chaperone and ER-associated apoptosis. GRP78, the ER chaperone, was up-regulated significantly in diabetic kidney compared to control. Furthermore, three hallmarks of ER-associated apoptosis, C/EBP homologous protein (CHOP), c-JUN NH2-terminal kinase (JNK) and caspase-12, were found to have activated in the diabetic kidney. Taken together, those results suggested that apoptosis induced by ER stress occurred in diabetic kidney, which may contribute to the development of diabetic nephropathy.
Insights
Endoplasmic reticulum stress contributes to kidney damage in diabetic nephropathy. This study found increased ER stress and apoptosis in the kidneys of diabetic rats, suggesting a role in disease development.
Area of Science:
- Nephrology
- Molecular Biology
- Endocrinology
Background:
- Diabetic complications are linked to endoplasmic reticulum (ER) stress.
- The role of ER stress in diabetic nephropathy-induced kidney injury remains unclear.
Purpose of the Study:
- To investigate the involvement of ER-associated apoptosis in streptozotocin-induced diabetic nephropathy in rats.
- To analyze key markers of ER stress and apoptosis in the kidneys of diabetic rats.
Main Methods:
- Streptozotocin-induced diabetic rat model.
- Assessment of albuminuria, kidney histology (H&E), and apoptosis (TUNEL assay).
- Immunohistochemistry, Western blot, and real-time PCR for ER stress markers (GRP78, CHOP, JNK, caspase-12).
Main Results:
- Diabetic rats exhibited signs of nephropathy and increased kidney apoptosis.
- Significant upregulation of the ER chaperone GRP78 was observed in diabetic kidneys.
- Key ER-associated apoptosis markers (CHOP, JNK, caspase-12) were activated in diabetic kidneys.
Conclusions:
- Apoptosis induced by ER stress occurs in the kidneys of diabetic rats.
- ER stress-mediated apoptosis may play a significant role in the pathogenesis of diabetic nephropathy.
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