ZNF580, a novel C2H2 zinc-finger transcription factor, interacts with the TGF-β signal molecule Smad2
Graduate School of Tianjin Medical University, Tianjin 300070, Peoples Republic of China. Cell Biology International
(Impact Factor: 1.93).
05/2011; 35(11):1153-7. DOI: 10.1042/CBI20110050
ZNF580 (gene ID 51157), a novel gene encoding a C2H2 (Cys2-His2) zinc-finger transcription factor, may be involved in the maintenance of vascular endothelium homoeostasis. To investigate the physiological role of the transcription factor ZNF580, we screened human foetal brain cDNA library with a yeast two-hybrid system and identified 14 proteins that interact with ZNF580. The interaction between ZNF580 and Smad2 was confirmed by co-immunoprecipitation. Co-localization between endogenous ZNF580 and Smad2 was mainly found in the nuclei of EA.hy926 endothelial cells with immunofluorescence and confocal microscopy. Our results suggest that ZNF580 is a binding partner of Smad2 and is involved in the signal transduction of the TGF-β (transforming growth factor-β) signalling pathway, which provides a basis for additional research to investigate the role of ZNF580 in the maintenance of vascular endothelium homoeostasis and the onset of atherosclerotic diseases.
Available from: Youichi Ogawa
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ABSTRACT: Zinc deficiency can be an inherited disorder, in which case it is known as acrodermatitis enteropathica (AE), or an acquired disorder caused by low dietary intake of zinc. Even though zinc deficiency diminishes cellular and humoral immunity, patients develop immunostimulating skin inflammation. Here, we have demonstrated that despite diminished allergic contact dermatitis in mice fed a zinc-deficient (ZD) diet, irritant contact dermatitis (ICD) in these mice was more severe and prolonged than that in controls. Further, histological examination of ICD lesions in ZD mice revealed subcorneal vacuolization and epidermal pallor, histological features of AE. Consistent with the fact that ATP release from chemically injured keratinocytes serves as a causative mediator of ICD, we found that the severe ICD response in ZD mice was attenuated by local injection of soluble nucleoside triphosphate diphosphohydrolase. In addition, skin tissue from ZD mice with ICD showed increased levels of ATP, as did cultured wild-type keratinocytes treated with chemical irritants and the zinc-chelating reagent TPEN. Interestingly, numbers of epidermal Langerhans cells (LCs), which play a protective role against ATP-mediated inflammatory signals, were decreased in ZD mice as well as samples from ZD patients. These findings suggest that upon exposure to irritants, aberrant ATP release from keratinocytes and impaired LC-dependent hydrolysis of nucleotides may be important in the pathogenesis of AE.
The Journal of clinical investigation 01/2012; 122(2):722-32. DOI:10.1172/JCI58618 · 13.22 Impact Factor
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ABSTRACT: ZNF580 is a novel C2H2 zinc-finger nuclear transcription factor with potential involvement in the transforming growth factor-β1 (TGF-β1) signal transduction pathway. Emerging evidence suggests that TGF-β1 can regulate endothelial nitric oxide synthase (eNOS) expression in endothelial cells. This study aimed to determine if ZNF580 mediated eNOS expression and participated in endothelial cell migration and proliferation via the TGF-β1/Smad2/ZNF580/eNOS signaling pathway. Overexpression/downexpression of ZNF580 in EAhy926 cells leads to the enhancement/decrease of eNOS expression. TGF-β1 downregulated both ZNF580 and eNOS at the mRNA and protein levels in concentration- and time-dependent manners. ZNF580 and eNOS downregulation induced by TGF-β1 was blocked by the specific TGF-β1 type I receptor ALK5 inhibitor, SB431542. Overexpression of ZNF580 attenuated TGF-β1-induced inhibition of EAhy926 cell growth and mobility, and vice versa. These results suggest that ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGF-β1/ALK5/Smad2 pathway, and thus plays a crucial role in vascular endothelial cells.
Molecular and Cellular Biochemistry 04/2014; 393(1-2). DOI:10.1007/s11010-014-2061-z · 2.39 Impact Factor
Available from: Jing Yang
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ABSTRACT: Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts.
Chemical Society Reviews 05/2015; 44(15). DOI:10.1039/C4CS00483C · 33.38 Impact Factor
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