Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications
Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease worldwide, affecting approximately 40% of individuals with type 2 diabetes (T2DM) and 30% of those with type 1 diabetes (T1DM). As the prevalence of diabetes continues to rise, the burden of...
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2024-12-01
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| author | Lyubomir Gaydarski Kristina Petrova Ivan Angushev Stancho Stanchev Alexandar Iliev Nikola Stamenov Vidin Kirkov Boycho Landzhov |
| author_facet | Lyubomir Gaydarski Kristina Petrova Ivan Angushev Stancho Stanchev Alexandar Iliev Nikola Stamenov Vidin Kirkov Boycho Landzhov |
| author_sort | Lyubomir Gaydarski |
| collection | DOAJ |
| description | Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease worldwide, affecting approximately 40% of individuals with type 2 diabetes (T2DM) and 30% of those with type 1 diabetes (T1DM). As the prevalence of diabetes continues to rise, the burden of DKD is expected to grow correspondingly. This review explores the roles of key molecular pathways, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling, in DKD pathogenesis and potential therapeutic applications. The apelinergic system, involving apelin and its receptor (APLNR), influences endothelial function, glucose metabolism, and renal health. Preclinical studies highlight its dual role in renal protection and injury through anti-inflammatory and antioxidant pathways, while other evidence suggests that it may exacerbate DKD through podocyte damage and angiogenesis. Similarly, the VEGF/VEGFR axis demonstrates a complex contribution to DKD, where VEGF-A promotes pathological angiogenesis and glomerular damage, but its inhibition requires careful modulation to prevent adverse effects. The NO/NOS system, integral to vascular and renal homeostasis, also exhibits altered activity in DKD, with reduced bioavailability linked to oxidative stress and inflammation. This review underscores the intricate interplay between these pathways in DKD, revealing both challenges and opportunities in their therapeutic targeting. Further research is essential to refine strategies and develop effective interventions for DKD management. |
| format | Article |
| id | doaj-art-34c81e24976b40139b3f3dc6c21dd828 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-34c81e24976b40139b3f3dc6c21dd8282025-01-24T13:23:50ZengMDPI AGBiomedicines2227-90592024-12-011315010.3390/biomedicines13010050Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic ImplicationsLyubomir Gaydarski0Kristina Petrova1Ivan Angushev2Stancho Stanchev3Alexandar Iliev4Nikola Stamenov5Vidin Kirkov6Boycho Landzhov7Department of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, BulgariaDepartment of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, BulgariaDepartment of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, BulgariaDepartment of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, BulgariaDepartment of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, BulgariaDepartment of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, BulgariaDepartment of Health Policy and Management, Faculty of Public Health ‘Prof. Dr. Tzekomir Vodenicharov’, Medical University of Sofia, 1527 Sofia, BulgariaDepartment of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, BulgariaDiabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease worldwide, affecting approximately 40% of individuals with type 2 diabetes (T2DM) and 30% of those with type 1 diabetes (T1DM). As the prevalence of diabetes continues to rise, the burden of DKD is expected to grow correspondingly. This review explores the roles of key molecular pathways, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling, in DKD pathogenesis and potential therapeutic applications. The apelinergic system, involving apelin and its receptor (APLNR), influences endothelial function, glucose metabolism, and renal health. Preclinical studies highlight its dual role in renal protection and injury through anti-inflammatory and antioxidant pathways, while other evidence suggests that it may exacerbate DKD through podocyte damage and angiogenesis. Similarly, the VEGF/VEGFR axis demonstrates a complex contribution to DKD, where VEGF-A promotes pathological angiogenesis and glomerular damage, but its inhibition requires careful modulation to prevent adverse effects. The NO/NOS system, integral to vascular and renal homeostasis, also exhibits altered activity in DKD, with reduced bioavailability linked to oxidative stress and inflammation. This review underscores the intricate interplay between these pathways in DKD, revealing both challenges and opportunities in their therapeutic targeting. Further research is essential to refine strategies and develop effective interventions for DKD management.https://www.mdpi.com/2227-9059/13/1/50diabetic kidney diseaseapelinapelin receptorvascular endothelial growth factorvascular endothelial growth factor receptorsnitric oxide |
| spellingShingle | Lyubomir Gaydarski Kristina Petrova Ivan Angushev Stancho Stanchev Alexandar Iliev Nikola Stamenov Vidin Kirkov Boycho Landzhov Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications Biomedicines diabetic kidney disease apelin apelin receptor vascular endothelial growth factor vascular endothelial growth factor receptors nitric oxide |
| title | Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications |
| title_full | Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications |
| title_fullStr | Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications |
| title_full_unstemmed | Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications |
| title_short | Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications |
| title_sort | exploring the molecular modalities in the pathogenesis of diabetic kidney disease with a focus on the potential therapeutic implications |
| topic | diabetic kidney disease apelin apelin receptor vascular endothelial growth factor vascular endothelial growth factor receptors nitric oxide |
| url | https://www.mdpi.com/2227-9059/13/1/50 |
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