التفاصيل البيبلوغرافية
| العنوان: |
Increased size of solid organs in patients with Chuvash polycythemia and in mice with altered expression of HIF-1α and HIF-2α. |
| المؤلفون: |
Yoon, Donghoon, Okhotin, David V., Kim, Bumjun, Okhotina, Yulia, Okhotin, Daniel J., Miasnikova, Galina Y., Sergueeva, Adelina I., Polyakova, Lydia A., Maslow, Alexei, Lee, Yonggu, Semenza, Gregg L., Prchal, Josef T., Gordeuk, Victor R. |
| المصدر: |
Journal of Molecular Medicine; May2010, Vol. 88 Issue 5, p523-530, 8p, 3 Charts, 2 Graphs |
| مصطلحات موضوعية: |
POLYCYTHEMIA, CELL growth, CELL proliferation, PROTEIN kinases, GENETIC disorders, HEREDITY |
| مستخلص: |
Chuvash polycythemia, the first hereditary disease associated with dysregulated oxygen-sensing to be recognized, is characterized by a homozygous germ-line loss-of-function mutation of the VHL gene ( VHL R200W) resulting in elevated hypoxia inducible factor (HIF)-1α and HIF-2α levels, increased red cell mass and propensity to thrombosis. Organ volume is determined by the size and number of cells, and the underlying molecular control mechanisms are not fully elucidated. Work from several groups has demonstrated that the proliferation of cells is regulated in opposite directions by HIF-1α and HIF-2α. HIF-1α inhibits cell proliferation by displacing MYC from the promoter of the gene encoding the cyclin-dependent kinase inhibitor, p21Cip1, thereby inducing its expression. In contrast, HIF-2α promotes MYC activity and cell proliferation. Here we report that the volumes of liver, spleen, and kidneys relative to body mass were larger in 30 individuals with Chuvash polycythemia than in 30 matched Chuvash controls. In Hif1a +/− mice, which are heterozygous for a null (knockout) allele at the locus encoding HIF-1α, hepatic HIF-2α mRNA was increased (2-fold) and the mass of the liver was increased, compared with wild-type littermates, without significant difference in cell volume. Hepatic p21 Cip1 mRNA levels were 9.5-fold lower in Hif1a +/− mice compared with wild-type littermates. These data suggest that, in addition to increased red cell mass, the sizes of liver, spleen, and kidneys are increased in Chuvash polycythemia. At least in the liver, this phenotype may result from increased HIF-2α and decreased p21Cip1 levels leading to increased hepatocyte proliferation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
