ArticleDiabetes2010
Inhibition of connective tissue growth factor overexpression in diabetic retinopathy by SERPINA3K via blocking the WNT/beta-catenin pathway.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 81 citations in OpenAlex.
- Beyond hyperglycaemia: diabetic retinopathy is a multifactorial complication of diabetes mellitus.Annals of medicine · 2026Review
- Review
- SerpinA3k Deficiency Ameliorates Experimental type 2 Diabetes.Cellular and molecular life sciences : CMLS · 2025Article
- Advances in Selenium and Related Compounds Inhibiting Multi-Organ Fibrosis.Drug design, development and therapy · 2025Review
- Investigation of the effect of belinostat on MCF-7 breast cancer stem cells via the Wnt, Notch, and Hedgehog signaling pathway.Saudi medical journal · 2024Article
- Role of Serine Protease Inhibitors A1 and A3 in Ocular Pathologies.Investigative ophthalmology & visual science · 2024Review
- The pathogenic role of succinate-SUCNR1: a critical function that induces renal fibrosis via M2 macrophage.Cell communication and signaling : CCS · 2024Article
- Aberrant Akt2 signaling in the RPE may contribute to retinal fibrosis process in diabetic retinopathy.Cell death discovery · 2023Article
- SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury.International journal of molecular sciences · 2023Article
- The versatile role of Serpina3c in physiological and pathological processes: a review of recent studies.Frontiers in endocrinology · 2023Review
- The Contribution of Wnt Signaling to Vascular Complications in Type 2 Diabetes Mellitus.International journal of molecular sciences · 2022Review
- Wnt/frizzled Signaling in Endothelium: A Major Player in Blood-Retinal- and Blood-Brain-Barrier Integrity.Cold Spring Harbor perspectives in medicine · 2022Review
- Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases.Acta pharmaceutica Sinica. B · 2022Review
- Wnt Signaling in Inner Blood-Retinal Barrier Maintenance.International journal of molecular sciences · 2021Review
- The effect of Wnt/β-catenin pathway on the scleral remolding in the mouse during form deprivation.International ophthalmology · 2021Article
- Diabetes-induced upregulation of kallistatin levels exacerbates diabetic nephropathy via RAS activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Oxidative stress upregulates Wnt signaling in human retinal microvascular endothelial cells through activation of disheveled.Journal of cellular biochemistry · 2019Article
- SerpinA3 in the Early Recognition of Acute Kidney Injury to Chronic Kidney Disease (CKD) transition in the rat and its Potentiality in the Recognition of Patients with CKD.Scientific reports · 2019Article
- Elevated Kallikrein-binding protein in diabetes impairs wound healing through inducing macrophage M1 polarization.Cell communication and signaling : CCS · 2019Article
- Wnt Signaling in vascular eye diseases.Progress in retinal and eye research · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveConnective tissue growth factor (CTGF) is a major fibrogenic factor. Increased retinal CTGF levels have been implicated to play a role in diabetic retinopathy. SERPINA3K is a serine proteinase inhibitor, and its levels were decreased in retinas with diabetic retinopathy. The purpose of this study was to investigate the role of SERPINA3K in the regulation of CTGF and fibrogenesis and its mechanism of action. RESEARCH DESIGN AND
methodsAdenovirus expressing SERPINA3K was injected intravitreally into streptozotocin-induced diabetic rats. CTGF expression was measured using Western blot analysis and real-time RT-PCR. Fibrosis was evaluated by quantifying retinal fibronectin using enzyme-linked immunosorbent assay. Wnt pathway activation was determined by phosphorylation of LDL receptor-related protein 6, a coreceptor of Wnt ligands, and stabilization of beta-catenin, an essential effector of the canonical Wnt pathway.
resultsAd-SERPINA3K attenuated the CTGF and fibronectin overexpression in retinas of diabetic rats. In cultured retinal cells, SERPINA3K blocked the overproduction of CTGF induced by high glucose. Dickkopf-1, a specific Wnt antagonist, also attenuated the high-glucose-induced CTGF overexpression, indicating a role of Wnt signaling in CTGF overexpression in diabetes. Similarly, increased SERPINA3K blocked Wnt pathway activation in diabetic retinas and in cells treated with high glucose. Further, SERPINA3K also attenuated the Wnt3a-induced activation of the canonical Wnt pathway and the overexpression of CTGF.
conclusionSERPINA3K is an antifibrogenic factor, and its antifibrogenic activity is through blocking the Wnt pathway. Decreased SERPINA3K levels may contribute to the fibrosis in diabetic retinopathy.
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