ArticleScientific reports2017
Inhibition of SHIP2 in CD2AP-deficient podocytes ameliorates reactive oxygen species generation but aggravates apoptosis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Advances in SRNS Gene Research: From Precision Classification to Precision Diagnosis and Treatment.Biomedicines · 2026Review
- TangNaikang Formula Alleviates Podocyte Injury in Diabetic Nephropathy by Modulating the SHIP2/PI3K/AKT Pathway.Journal of diabetes research · 2025Article
- Integrative analysis of Iso-Seq and RNA-seq reveals dynamic changes of alternative promoter, alternative splicing and alternative polyadenylation during Angiotensin II-induced senescence in rat primary aortic endothelial cells.Frontiers in genetics · 2023Article
- Ebselen enhances insulin sensitivity and decreases oxidative stress by inhibiting SHIP2 and protects from inflammation in diabetic mice.International journal of biological sciences · 2022Article
- Review
- Targeting SHIP1 and SHIP2 in Cancer.Cancers · 2021Review
- SHIPping out diabetes-Metformin, an old friend among new SHIP2 inhibitors.Acta physiologica (Oxford, England) · 2020Review
- The impact of phosphoinositide 5-phosphatases on phosphoinositides in cell function and human disease.Journal of lipid research · 2019Review
- Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Protective Effects of Specneuzhenide on Renal Injury in Rats with Diabetic Nephropathy.Open medicine (Warsaw, Poland) · 2019Article
- Upregulation of SHIP2 participates in the development of breast cancer via promoting Wnt/β-catenin signaling.OncoTargets and therapy · 2019Article
- Puromycin aminonucleoside triggers apoptosis in podocytes by inducing endoplasmic reticulum stress.Kidney research and clinical practice · 2018Article
- Erzhi Formula Extracts Reverse Renal Injury in Diabetic Nephropathy Rats by Protecting the Renal Podocytes.Evidence-based complementary and alternative medicine : eCAM · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Lack of CD2-associated protein (CD2AP) in mice increases podocyte apoptosis and leads to glomerulosclerosis and renal failure. We showed previously that SHIP2, a negative regulator of the PI3K/AKT signalling pathway, interacts with CD2AP. Here, we found that the expression level and activity of SHIP2 and production of reactive oxygen species (ROS) are increased in cultured CD2AP knockout (CD2AP-/-) mouse podocytes. Oxidative stress was also increased in CD2AP-/- mouse glomeruli in vivo. We found that puromycin aminonucleoside (PA), known to increase ROS production and apoptosis, increases SHIP2 activity and reduces CD2AP expression in cultured human podocytes. PDK1 and CDK2, central regulators of AKT, were downregulated in CD2AP-/- or PA-treated podocytes. Downregulation of PDK1 and CDK2, ROS generation and apoptosis were prevented by CD2AP overexpression in both models. Notably, inhibition of SHIP2 activity with a small molecule inhibitor AS1949490 ameliorated ROS production in CD2AP-/- podocytes, but, surprisingly, further reduced PDK1 expression and aggravated apoptosis. AKT- and ERK-mediated signalling was diminished and remained reduced after AS1949490 treatment in the absence of CD2AP. The data suggest that inhibition of the catalytic activity of SHIP2 is beneficial in reducing oxidative stress, but leads to deleterious increase in apoptosis in podocytes with reduced expression of CD2AP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.