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Improving the Dysregulation of FoxO1 Activity Is a Potential Therapy for Alleviating Diabetic Kidney Disease
1Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Abstract:
A substantial proportion of patients with diabetes will develop kidney disease. Diabetic kidney disease (DKD) is one of the most serious complications in diabetic patients and the leading cause of end-stage kidney disease worldwide. Although some mechanisms have been revealed to contribute to the understanding of the pathogenesis of DKD and some drugs currently in use have been shown to be beneficial, prevention and management of DKD remain tricky and challenging. FoxO1 transcriptional factor is a crucial regulator of cellular homeostasis and posttranslational modification is a major mechanism to alter FoxO1 activity. There is increasing evidence that FoxO1 is involved in the regulation of various cellular processes such as stress resistance, autophagy, cell cycle arrest, and apoptosis, thereby playing an important role in the pathogenesis of DKD. Improving the dysregulation of FoxO1 activity by natural compounds, synthetic drugs, or manipulation of gene expression may attenuate renal cell injury and kidney lesion in the cells cultured under a high-glucose environment and in diabetic animal models. The available data imply that FoxO1 may be a potential clinical target for the prevention and treatment of DKD.
Insights
Diabetic kidney disease (DKD) affects many diabetes patients. Targeting the FoxO1 protein may offer new ways to prevent and treat this serious kidney complication.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Diabetic kidney disease (DKD) is a major complication of diabetes and a leading cause of end-stage kidney disease globally.
- Current prevention and management strategies for DKD are challenging despite some understanding of its pathogenesis.
Purpose of the Study:
- To explore the role of the FoxO1 transcriptional factor in the pathogenesis of diabetic kidney disease.
- To investigate the potential of targeting FoxO1 for the prevention and treatment of DKD.
Main Methods:
- Review of existing evidence on FoxO1's role in cellular processes relevant to DKD.
- Analysis of studies involving high-glucose environments and diabetic animal models.
Main Results:
- FoxO1 is a key regulator of cellular homeostasis, with its activity modulated by posttranslational modifications.
- Evidence suggests FoxO1 is involved in stress resistance, autophagy, cell cycle arrest, and apoptosis, all implicated in DKD pathogenesis.
- Modulating FoxO1 activity showed potential in attenuating renal cell injury in vitro and in vivo.
Conclusions:
- FoxO1 plays a significant role in the development of diabetic kidney disease.
- Targeting FoxO1 through various interventions may offer a promising therapeutic strategy for DKD.
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