ArticleDiabetologia2009
Overproduction of phosphoprotein enriched in diabetes (PED) induces mesangial expansion and upregulates protein kinase C-beta activity and TGF-beta1 expression.
Article in Diabetologia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Adrenergic signaling in heart failure and cardiovascular aging.Maturitas · 2016Review
- Phosphoprotein enriched in astrocytes (PEA)-15: a potential therapeutic target in multiple disease states.Pharmacology & therapeutics · 2014Review
- Blocking αVβ3 integrin ligand occupancy inhibits the progression of albuminuria in diabetic rats.Journal of diabetes research · 2014Article
- Key roles for the lipid signaling enzyme phospholipase d1 in the tumor microenvironment during tumor angiogenesis and metastasis.Science signaling · 2012Article
- Identification of nephropathy candidate genes by comparing sclerosis-prone and sclerosis-resistant mouse strain kidney transcriptomes.BMC nephrology · 2012Article
- PED/PEA-15 induces autophagy and mediates TGF-beta1 effect on muscle cell differentiation.Cell death and differentiation · 2012Article
- Age-related impairment in insulin release: the essential role of β(2)-adrenergic receptor.Diabetes · 2012Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisOverproduction of phosphoprotein enriched in diabetes (PED, also known as phosphoprotein enriched in astrocytes-15 [PEA-15]) is a common feature of type 2 diabetes and impairs insulin action in cultured cells and in mice. Nevertheless, the potential role of PED in diabetic complications is still unknown.
methodsWe studied the effect of PED overproduction and depletion on kidney function in animal and cellular models.
resultsTransgenic mice overexpressing PED (PEDTg) featured age-dependent increases of plasma creatinine levels and urinary volume, accompanied by expansion of the mesangial area, compared with wild-type littermates. Serum and kidney levels of TGF-beta1 were also higher in 6- and 9-month-old PEDTg. Overexpression of PED in human kidney 2 cells significantly increased TGF-beta1 levels, SMAD family members (SMAD)2/3 phosphorylation and fibronectin production. Opposite results were obtained following genetic silencing of PED in human kidney 2 cells by antisense oligonucleotides. Inhibition of phospholipase D and protein kinase C-beta by 2-butanol and LY373196 respectively reduced TGF-beta1, SMAD2/3 phosphorylation and fibronectin production. Moreover, inhibition of TGF-beta1 receptor activity and SMAD2/3 production by SB431542 and antisense oligonucleotides respectively reduced fibronectin secretion by about 50%. TGF-beta1 circulating levels were significantly reduced in Ped knockout mice and positively correlated with PED content in peripheral blood leucocytes of type 2 diabetic patients. CONCLUSIONS/
interpretationThese data indicate that PED regulates fibronectin production via phospholipase D/protein kinase C-beta and TGF-beta1/SMAD pathways in kidney cells. Raised PED levels may therefore contribute to the abnormal accumulation of extracellular matrix and renal dysfunction in diabetes.
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