ArticleOncotarget2016
CDK5 promotes renal tubulointerstitial fibrosis in diabetic nephropathy via ERK1/2/PPARγ pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Approach to Studies on Podocyte Lesions Mediated by Hyperglycemia: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Arg913Gln variation of SLC12A3 gene is associated with diabetic nephropathy in type 2 diabetes and Gitelman syndrome: a systematic review.BMC nephrology · 2019Pooled it
- Roles of the peroxisome proliferator-activated receptors (PPARs) in the pathogenesis of diabetic kidney disease (DKD).Cell death discovery · 2026Review
- CDK5: Insights into its roles in diseases.Molecular biology reports · 2025Review
- MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4.World journal of diabetes · 2024Article
- The epithelial-mesenchymal plasticity landscape: principles of design and mechanisms of regulation.Nature reviews. Genetics · 2023Review
- Cyclin G1 induces maladaptive proximal tubule cell dedifferentiation and renal fibrosis through CDK5 activation.The Journal of clinical investigation · 2022Article
- Ocular expression of cyclin-dependent kinase 5 in patients with proliferative diabetic retinopathy.Journal of diabetes investigation · 2022Article
- Peroxisome Proliferator-Activated Receptor Gene Knockout Promotes Podocyte Injury in Diabetic Mice.BioMed research international · 2022Article
- The cyclin dependent kinase inhibitor Roscovitine prevents diet-induced metabolic disruption in obese mice.Scientific reports · 2021Article
- High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct.Scientific reports · 2021Article
- Lipopolysaccharide-induced inflammation in human peritoneal mesothelial cells is controlled by ERK1/2-CDK5-PPARγ axis.Annals of translational medicine · 2021Article
- Role of Metabolic Reprogramming in Epithelial⁻Mesenchymal Transition (EMT).International journal of molecular sciences · 2019Review
- Role of sirtuin-1 in diabetic nephropathy.Journal of molecular medicine (Berlin, Germany) · 2019Review
- The non-neuronal cyclin-dependent kinase 5 is a fibrotic mediator potentially implicated in systemic sclerosis and a novel therapeutic target.Oncotarget · 2018Article
- MicroRNA-27a promotes podocyte injury via PPARγ-mediated β-catenin activation in diabetic nephropathy.Cell death & disease · 2017Article
- MicroRNA-27a promotes renal tubulointerstitial fibrosis via suppressing PPARγ pathway in diabetic nephropathy.Oncotarget · 2016Article
- Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes.Journal of diabetes research · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin-dependent kinase 5 (CDK5) has been documented in podocyte injuries in diabetic nephropathy (DN), however its role in renal tubular epithelial cells has not been elucidated. We report here that CDK5 is detrimental and promotes tubulointerstitial fibrosis (TIF) via the extracellular signal-regulated kinase 1/2 (ERK1/2)/peroxisome proliferator-activated receptor gamma (PPRAγ) pathway in DN. In high glucose cultured NRK52E cells, blocking CDK5 activity inhibited epithelial-to-mesenchymal transition (EMT) and fibrosis via ERK1/2/PPARγ pathway. In diabetic rats, CDK5 inhibitor roscovitine decreased renal fibrosis and improved renal function as demonstrated by a decrease in levels of blood urine nitrogen (BUN), serum creatinine and β2-microglobulin. Further studies revealed that improved renal fibrosis and function in diabetic rats were associated with inactivation of ERK1/2 and PPARγ signaling pathways. In late staged DN patients, the upregulation of CDK5 and p35 activated phosphorylated ERK1/2 and PPARγ, leading to decreased levels of E-cadherin but increased Vimentin and Collagen IV. Accordingly, renal fibrosis and function were worsened as revealed by decreased estimated glomerular filtration rate (eGFR) and increased serum BUN, creatinine, β2-microglobulin, 24-hour proteinuria and urine albumin to creatinine ratio (UACR). These findings demonstrate a novel mechanism that CDK5 increases tubulointerstitial fibrosis by activating the ERK1/2/PPARγ pathway and EMT in DN. CDK5 might have therapeutic potential in diabetic nephropathy.
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