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The molecular mechanism underlying angiogenesis in a mouse model of chronic kidney disease after ischemic stroke
Fang Wang1, Liangxiang Lu2, Jialun Feng2
1Ganzhou People's Hospital (Nanfang Hospital, Ganzhou) Ganzhou 341000, Jiangxi, China.
Objectives:
The study aims to establish a reliable chronic kidney disease (CKD) mouse model by examining the effects of an adenine-containing diet on renal function and pathology. It also explores the impact of CKD on motor function and infarct volume following cerebral infarction and investigates the role of calcium in modulating the AMPK/SIRT1/HIF1-α signaling pathways.
Method:
The CKD mouse model was induced through an adenine-enriched diet. Renal function impairment was assessed by analyzing blood samples for creatinine and blood urea nitrogen levels at 0 and 6 weeks. Pathologic changes in renal tissue were examined. The study also evaluated motor function, infarct volume, survival rates, body weight changes, and functional assessments. Additionally, cerebral cortex angiogenesis was assessed in the context of ischemic stroke.
Result:
The CKD mouse model showed significant renal tissue alterations, including luminal dilation, glomerular hypertrophy, fibrosis, and inflammatory infiltration. There was a notable reduction in angiogenic markers in the CKD group compared to controls. The study also found increased cerebral calcium levels and altered expression of AMPK, SIRT1, HIF1-α, and VEGF in the CKD group.
Conclusions:
The research successfully created the CKD mouse model and emphasized the disease's many effects, including its influence on neurological disorders. The results provide an understanding of the molecular processes behind changes brought on by CKD and may have consequences for angiogenesis and signaling pathway-focused therapeutic approaches.
Insights
This study successfully created a chronic kidney disease (CKD) mouse model using an adenine diet, revealing its impact on renal pathology and neurological function, particularly angiogenesis.
Area of Science:
- Nephrology
- Neurology
- Molecular Biology
Background:
- Chronic kidney disease (CKD) is a global health concern with complex systemic effects.
- Understanding CKD's impact on other organ systems, like the brain, is crucial for comprehensive management.
Purpose of the Study:
- To establish a reliable adenine-induced chronic kidney disease (CKD) mouse model.
- To investigate the effects of CKD on renal function, pathology, and cerebral infarction outcomes.
- To explore the role of calcium and specific signaling pathways (AMPK/SIRT1/HIF1-α) in CKD.
Main Methods:
- Induction of CKD in mice using an adenine-enriched diet.
- Assessment of renal function via creatinine and blood urea nitrogen levels.
- Evaluation of motor function, infarct volume, and cerebral cortex angiogenesis post-ischemic stroke.
Main Results:
- The adenine diet successfully induced CKD with significant renal tissue alterations, including fibrosis and inflammation.
- CKD mice exhibited reduced angiogenic markers and altered expression of AMPK, SIRT1, HIF1-α, and VEGF.
- Increased cerebral calcium levels were observed in the CKD model.
Conclusions:
- The established CKD mouse model effectively demonstrates the disease's multifaceted impact, including neurological complications.
- Findings highlight potential molecular mechanisms underlying CKD-associated changes in angiogenesis and signaling pathways.
- This model provides a foundation for developing targeted therapeutic strategies for CKD and its sequelae.
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