1998 Fiscal Year Final Research Report Summary
Molecular Studies of Prostanoid Receptors in the Kidney
| Project/Area Number |
09671163
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TANAKA Issei Kyoto University Graduate School of Medicine, Dept.of Medicine and Clinical Science, Associate Professor, 医学研究科, 助教授 (80179738)
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| Co-Investigator(Kenkyū-buntansha) |
MUKOYAMA Masashi Research Institute for Production Development, Researcher, 研究員 (40270558)
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| Project Period (FY) |
1997 – 1998
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| Keywords | PGE_2 / EP3 / EP1 / EP4 / IP / mesangial cell / gene / adrenomedullin |
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| Research Abstract |
PGE_2 receptor subtype EP3 is widely distributed in the renal tubules. However the precise analysis of its abundant isoform has not been done yet. We clarified that the human EP3 gene spanned more than 80 kb and was composed of 10 exons. The EP3 gene formed 9 distinct mRNAs encoding 8 EP3 isoforms. The transcription initiation sites of the EP3 gene were mapped 227 to -231 bp upstream of the ATG start codon. The 360-bp 5'-flanking region contained a TATA box-like sequence, a GC box, and several cis-acting regulatory elements. We also indicated that prostacyclin receptor is expressed in human megakaryocytes and is upregulated by cytokines involved in thrombopoiesis or inflammation. In rat mesangial cells, EP1 and EP4 mRNAs were detected and EP1 antagonists dose-dependently attenuated high glucose-induced ^3H-thymidine uptake in mesangial cells. PGE_2-induced cAMP synthesis was significantly attenuated under high glucose condition. Therefore, the increase in DNA synthesis in mesangial cells under high glucose conditions can be explained in part by the high glucose-induced inhibition of cAMP production via EP4, which augments EP1 function in conjunction with overproduction of PGE_2. We found that adrenomedullin, acting as autocrine/paracrine regulator, exerts an antiproliferative action on mesangial cells. AT2 receptor is expressed in mesangial cells in a growth-dependent manner and its inhibitory role of mesangial cell growth in WKY was suggested.
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