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Intronic CArG box regulates cysteine-rich protein 2 expression in the adult but not in developing vasculature.

ABSTRACT: An absence of cysteine-rich protein 2 (CRP2) enhances vascular smooth muscle cell (VSMC) migration and increases neointima formation after arterial injury; therefore, CRP2 plays an important role in the response to vascular injury. The goal of the present study was to elucidate the molecular mechanisms that preserve CRP2 expression in the adult vasculature and thus might serve to inhibit the response to injury.We generated a series of transgenic mice harboring potential Csrp2 regulatory regions with a lacZ reporter. We determined that the 12-kb first intron was necessary for transgene activity in adult but not in developing vasculature. Within the intron we identified a 6.3-kb region that contains 2 CArG boxes. Serum response factor preferentially bound to CArG2 box in gel mobility shift and chromatin immunoprecipitation assays; additionally, serum response factor coactivator myocardin factors activated CRP2 expression via the CArG2 box. Mutational analysis revealed that CArG2 box was important in directing lacZ expression in VSMC of adult vessels.Although CRP2 expression during development is independent of CArG box regulatory sites, CRP2 expression in adult VSMC requires CArG2 element within the first intron. Our results suggest that distinct mechanisms regulate CRP2 expression in VSMC that are controlled by separate embryonic and adult regulatory modules.

SUBMITTER: Chen CH

PROVIDER: S-EPMC2841712 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Intronic CArG box regulates cysteine-rich protein 2 expression in the adult but not in developing vasculature.

Chen Chung-Huang CH Wu Meng-Ling ML Lee Yi-Chung YC Layne Matthew D MD Yet Shaw-Fang SF

Arteriosclerosis, thrombosis, and vascular biology 20100114 4

<h4>Objective</h4>An absence of cysteine-rich protein 2 (CRP2) enhances vascular smooth muscle cell (VSMC) migration and increases neointima formation after arterial injury; therefore, CRP2 plays an important role in the response to vascular injury. The goal of the present study was to elucidate the molecular mechanisms that preserve CRP2 expression in the adult vasculature and thus might serve to inhibit the response to injury.<h4>Methods and results</h4>We generated a series of transgenic mice ...[more]

PMID: 20075421

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Project description:Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs) in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs) in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTP?, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTP? were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTP? promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5) and postnatal (P0, P3, P7) kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage), and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTP? immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1) VE-PTP and PTP? are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2) their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3) peritubular capillary VE-PTP expression is down-regulated in adult kidneys, suggesting a role of VE-PTP in the development of peritubular capillaries.

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Intronic CArG box regulates cysteine-rich protein 2 expression in the adult but not in developing vasculature.

Publications

Intronic CArG box regulates cysteine-rich protein 2 expression in the adult but not in developing vasculature.

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