Transcriptional regulation and cellular trafficking of aquaporin-2 water channel
| Project/Area Number |
17590841
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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 | Jichi Medical University |
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Principal Investigator |
ISHIKAWA San-e Jichi Medical University, School of Medicine, Professor, 医学部, 教授 (70112620)
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| Co-Investigator(Kenkyū-buntansha) |
TAMEMOTO Hiroyuki Jichi Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (90292630)
FUNAYAMA Hiroshi Jichi Medical University, School of Medicine, Instructor, 医学部, 助手 (40296116)
SAITO Takako Jichi Medical University, School of Medicine, Research associate, 医学部, 研究員 (90296103)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Vasopressin / Aquaporin-2 / Osmolality / Transcriptional regulation / Promoter / Impaired water excretion / プロモーター活性 |
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| Research Abstract |
We had examined the regulatory mechanism of aquaporin-2 (AQP-2) water channel in both in vitro and in vivo systems. (1) in vitro study : Various fragments of 5'-flanking region of murine AQP-2 gene up to -9.5 kb were cloned into a luciferase (Luc) reporter plasmid, and they were transiently transfected into MDCK or mIMCD3 cells. Hypertonicity-response enhancers were at least resided at two segments, namely tonicity-response enhancer (TonE)(-570〜-560bp) and unknown region between -6.1 and -4.3 kb of the 5'-flanking region of AQP-2 gene. The latter had the different structure and mechanism of response to hypertonicity from those of TonE. They regulated AQP-2 transcriptional regulation independently of arginine vasopressin (AVP). The region between -6.1 and -4.3 kb dominantly received hypertonicity signal, but its regulation further collaborated with TonE to activate the transcription of AQP-2 gene. On the contrary, TonE per se could be involved in hypotonicity-regulated AQP-2 transcripti
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on. Hypotonicity per se did not alter basal activity of Luc, but attenuated cAMP-induced Luc activity. This action was mediated through JNK. These findings indicate that tonicity-response enhancers are located at the 5'-flanking region of AQP-2, and regulate hyper- and hypotonicity-induced AQP-2 transcription. (2) in vivo study : We examined whether aging affects kidney expression of AQP-2 in glucocorticoid-deficient rats. Impaired water excretion was found in glucocorticoid-deficient rats, but its impairment was much serious in the aged rats compared with the young ones. Kidney AQP-2 expression was reduced in the aged rats. Plasma AVP was not sufficiently suppressed in the glucocorticoid-deficient t rats, and the expression of kidney AQP-2 mRNA and protein were rather upregulated in the aged rats with glucocorticoid deficiency. The present findings indicate that the upregulation of AQP-2 against aging plays a crucial role in persistent impairment in water excretion, dependent upon non-suppressible release of AVP, in aged rats with glucocorticoid deficiency. Less
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(3 results)
Research Products
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