ArticlePloS one2010
In vivo delivery of Gremlin siRNA plasmid reveals therapeutic potential against diabetic nephropathy by recovering bone morphogenetic protein-7.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 65 citations in OpenAlex.
- Adenosine ACells · 2025Article
- Small interfering RNA (siRNA) as a potential gene silencing strategy for diabetes and associated complications: challenges and future perspectives.Journal of diabetes and metabolic disorders · 2024Review
- Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy.International journal of biological sciences · 2024Article
- Cellular crosstalk of mesangial cells and tubular epithelial cells in diabetic kidney disease.Cell communication and signaling : CCS · 2023Review
- Epigenetic Modulation of Gremlin-1/NOTCH Pathway in Experimental Crescentic Immune-Mediated Glomerulonephritis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Gremlin: a complex molecule regulating wound healing and fibrosis.Cellular and molecular life sciences : CMLS · 2021Review
- Baicalin attenuates adriamycin-induced nephrotic syndrome by regulating fibrosis procession and inflammatory reaction.Genes & genomics · 2021Article
- VEGFR2 Blockade Improves Renal Damage in an Experimental Model of Type 2 Diabetic Nephropathy.Journal of clinical medicine · 2020Article
- Gremlin is a potential target for posterior capsular opacification.Cell cycle (Georgetown, Tex.) · 2019Article
- Pregnancy protects the kidney from acute ischemic injury.Scientific reports · 2018Article
- Bone Morphogenetic Protein-Based Therapeutic Approaches.Cold Spring Harbor perspectives in biology · 2018Review
- Acute Kidney Injury and Progression of Diabetic Kidney Disease.Advances in chronic kidney disease · 2018Review
- Gremlin Regulates Podocyte Apoptosis via Transforming Growth Factor-β (TGF-β) Pathway in Diabetic Nephropathy.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Gremlin Regulates Tubular Epithelial to Mesenchymal Transition via VEGFR2: Potential Role in Renal Fibrosis.Frontiers in pharmacology · 2018Article
- Diabetic Nephropathy: a Tangled Web to Unweave.Cardiovascular drugs and therapy · 2017Review
- Gremlin1 plays a key role in kidney development and renal fibrosis.American journal of physiology. Renal physiology · 2017Article
- Gremlin is a key pro-fibrogenic factor in chronic pancreatitis.Journal of molecular medicine (Berlin, Germany) · 2015Article
- Gremlin1 and chronic pancreatitis: a new clinical target and biomarker?Journal of molecular medicine (Berlin, Germany) · 2015Article
- Therapeutic targets for treating fibrotic kidney diseases.Translational research : the journal of laboratory and clinical medicine · 2015Review
- Bone morphogenetic proteins and their antagonists: current and emerging clinical uses.British journal of pharmacology · 2014Review
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic nephropathy is a complex and poorly understood disease process, and our current treatment options are limited. It remains critical, then, to identify novel therapeutic targets. Recently, a developmental protein and one of the bone morphogenetic protein antagonists, Gremlin, has emerged as a novel modulator of diabetic nephropathy. The high expression and strong co-localization with transforming growth factor-beta1 in diabetic kidneys suggests a role for Gremlin in the pathogenesis of diabetic nephropathy. We have constructed a gremlin siRNA plasmid and have examined the effect of Gremlin inhibition on the progression of diabetic nephropathy in a mouse model. CD-1 mice underwent uninephrectomy and STZ treatment prior to receiving weekly injections of the plasmid. Inhibition of Gremlin alleviated proteinuria and renal collagen IV accumulation 12 weeks after the STZ injection and inhibited renal cell proliferation and apoptosis. In vitro experiments, using mouse mesangial cells, revealed that the transfect ion of gremlin siRNA plasmid reversed high glucose induced abnormalities, such as increased cell proliferation and apoptosis and increased collagen IV production. The decreased matrix metalloprotease level was partially normalized by transfection with gremlin siRNA plasmid. Additionally, we observed recovery of bone morphogenetic protein-7 signaling activity, evidenced by increases in phosphorylated Smad 5 protein levels. We conclude that inhibition of Gremlin exerts beneficial effects on the diabetic kidney mainly through maintenance of BMP-7 activity and that Gremlin may serve as a novel therapeutic target in the management of diabetic nephropathy.
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