ArticleMolecular medicine reports2015
Klotho gene delivery ameliorates renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats by suppressing the Rho-associated coiled-coil kinase signaling pathway.
Article in Molecular medicine reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Pharmaceutical Strategies for Translating Klotho-Based Therapeutics: From Biologic Developability to Advanced Delivery Systems.Pharmaceutics · 2026Review
- α-Klotho Supplementation Mitigates Cumulative Exercise-Induced Fatigue via Coordinated NRF2-Mediated Antioxidant Defense and AKT/GS-Driven Hepatic Glycogen Supercompensation in Mice.International journal of molecular sciences · 2025Article
- Multi-Target Therapeutic Potential of Arctii Fructus Lignans in Diabetes Mellitus and Its Complications: A Mechanistic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Soluble Klotho protects against glomerular injury through regulation of ER stress response.Communications biology · 2023Article
- Klotho, Oxidative Stress, and Mitochondrial Damage in Kidney Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Klotho's impact on diabetic nephropathy and its emerging connection to diabetic retinopathy.Frontiers in endocrinology · 2023Review
- ROCK2-induced metabolic rewiring in diabetic podocytopathy.Communications biology · 2022Article
- lncRNA MALAT1 Promotes Renal Fibrosis in Diabetic Nephropathy by Targeting the miR-2355-3p/IL6ST Axis.Frontiers in pharmacology · 2021Article
- Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy.PloS one · 2021Article
- Nano Ellagic Acid Counteracts Cisplatin-Induced Upregulation in OAT1 and OAT3: A Possible Nephroprotection Mechanism.Molecules (Basel, Switzerland) · 2020Article
- Arctiin attenuates high glucose-induced human retinal capillary endothelial cell proliferation by regulating ROCK1/PTEN/PI3K/Akt/VEGF pathway in vitro.Journal of cellular and molecular medicine · 2020Article
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- EGCG Attenuates Renal Damage via Reversing Klotho Hypermethylation in Diabetic db/db Mice and HK-2 Cells.Oxidative medicine and cellular longevity · 2020Article
- αKlotho-FGF23 interactions and their role in kidney disease: a molecular insight.Cellular and molecular life sciences : CMLS · 2019Review
- Klotho protein supplementation reduces blood pressure and renal hypertrophy in db/db mice, a model of type 2 diabetes.Acta physiologica (Oxford, England) · 2019Article
- Reduction of cellular stress is essential for Fibroblast growth factor 1 treatment for diabetic nephropathy.Journal of cellular and molecular medicine · 2018Article
- Empagliflozin, SGLTNaunyn-Schmiedeberg's archives of pharmacology · 2018Article
- Role of Fibroblast Growth Factor-23 in Innate Immune Responses.Frontiers in endocrinology · 2018Review
- Diabetic nephropathy: Time to withhold development and progression - A review.Journal of advanced research · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The present study aimed to investigate whether klotho gene delivery attenuated renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats. A recombinant adeno-associated virus (rAAV) carrying mouse klotho full-length cDNA (rAAV.mKL), was constructed for in vivo investigation of klotho expression. Diabetes was induced in rats by a single tail vein injection of 60 mg/kg streptozotocin. Subsequently, the diabetic rats received an intravenous injection of rAAV.mKL, rAAV.green fluorescent protein (GFP) or phosphate-buffered saline (PBS). The Sprague-Dawley rat group received PBS and served as the control group. After 12 weeks, all the rats were sacrificed and ELISA, immunohistochemical and histological analyses, fluorescence microscopy, semi-quantitative reverse transcription-polymerase chain reaction and western blottin were performed. A single dose of rAAV.mKL was found to prevent the progression of renal hypertrophy and fibrosis for at least 12 weeks (duration of study). Klotho expression was suppressed in the diabetic rats, but was increased by rAAV.mKL delivery. rAAV.mKL significantly suppressed diabetes-induced renal hypertrophy and histopathological changes, reduced renal collagen fiber generation and decreased kidney hypertrophy index. In addition, rAAV.mKL decreased the protein expression levels of fibronectin and vimentin, while it downregulated the mRNA expression and activity of Rho-associated coiled-coil kinase (ROCK)I in the kidneys of the diabetic rats. These results indicated that klotho gene delivery ameliorated renal hypertrophy and fibrosis in diabetic rats, possibly by suppressing the ROCK signaling pathway. This may offer a novel approach for the long-term control and renoprotection of diabetes.
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