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Cyst Formation in Kidney via B-Raf Signaling in the PKD2 Transgenic Mice
DC Field | Value | Language |
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dc.contributor.author | Park, Eun Young | - |
dc.contributor.author | Sung, Young Hoon | - |
dc.contributor.author | Yang, Moon Hee | - |
dc.contributor.author | Noh, Ji Yeun | - |
dc.contributor.author | Lee, Tae Young | - |
dc.contributor.author | Yoo, Kyung Hyun | - |
dc.contributor.author | Kim, Ingyu | - |
dc.contributor.author | Oh, Goo Taeg | - |
dc.contributor.author | Ahn, Curie | - |
dc.contributor.author | Park, Jong Hoon | - |
dc.contributor.author | Lee, Han-Woong | - |
dc.contributor.author | Seong, Je Kyung | - |
dc.contributor.author | Hwang, Young-Hwan | - |
dc.contributor.author | Roh, Kyung Jin | - |
dc.contributor.author | Yook, Yeon Joo | - |
dc.contributor.author | Park, So Young | - |
dc.date.accessioned | 2012-05-23T07:24:32Z | - |
dc.date.available | 2012-05-23T07:24:32Z | - |
dc.date.issued | 2009-03-13 | - |
dc.identifier.citation | JOURNAL OF BIOLOGICAL CHEMISTRY; Vol.284 11; 7214-7222 | ko_KR |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://hdl.handle.net/10371/76344 | - |
dc.description.abstract | The pathogenic mechanisms of human autosomal dominant polycystic kidney disease (ADPKD) have been well known to include the mutational inactivation of PKD2. Although haploinsufficiency and loss of heterozygosity at the Pkd2 locus can cause cyst formation in mice, polycystin-2 is frequently expressed in the renal cyst of human ADPKD, raising the possibility that deregulated activation of PKD2 may be associated with the cystogenesis of human ADPKD. To determine whether increased PKD2 expression is physiologically pathogenic, we generated PKD2-overexpressing transgenic mice. These mice developed typical renal cysts and an increase of proliferation and apoptosis, which are reflective of the human ADPKD phenotype. These manifestations were first observed at six months, and progressed with age. In addition, we found that ERK activation was induced by PKD2 overexpression via B-Raf signaling, providing a possible molecular mechanism of cystogenesis. In PKD2 transgenic mice, B-Raf/MEK/ERK sequential signaling was up-regulated. Additionally, the transgenic human polycystin-2 partially rescues the lethality of Pkd2 knock-out mice and therefore demonstrates that the transgene generated a functional product. Functional strengthening or deregulated activation of PKD2 may be a direct cause of ADPKD. The present study provides evidence for an in vivo role of overexpressed PKD2 in cyst formation. This transgenic mouse model should provide new insights into the pathogenic mechanism of human ADPKD. | ko_KR |
dc.description.sponsorship | This work was supported by National Research Laboratory Grant R0A-2005-
000-10101-0, the SRC/ERC program of the KOSEF grant funded by MEST (Research Center for Womens Disease), and 21C Frontier Projects (Functional Human Genome Project, M106KB010014-07K0201-01410 and Brain Research Center, M103KV010025-07K2201-02510) from the MEST. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | ko_KR |
dc.title | Cyst Formation in Kidney via B-Raf Signaling in the PKD2 Transgenic Mice | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 박은영 | - |
dc.contributor.AlternativeAuthor | 성영훈 | - |
dc.contributor.AlternativeAuthor | 양문희 | - |
dc.contributor.AlternativeAuthor | 노지연 | - |
dc.contributor.AlternativeAuthor | 박소영 | - |
dc.contributor.AlternativeAuthor | 이태영 | - |
dc.contributor.AlternativeAuthor | 육연주 | - |
dc.contributor.AlternativeAuthor | 유경현 | - |
dc.contributor.AlternativeAuthor | 노경진 | - |
dc.contributor.AlternativeAuthor | 김인규 | - |
dc.contributor.AlternativeAuthor | 황영환 | - |
dc.contributor.AlternativeAuthor | 오구택 | - |
dc.contributor.AlternativeAuthor | 성제경 | - |
dc.contributor.AlternativeAuthor | 안규리 | - |
dc.contributor.AlternativeAuthor | 이한웅 | - |
dc.contributor.AlternativeAuthor | 박종훈 | - |
dc.identifier.doi | 10.1074/jbc.M805890200 | - |
dc.citation.journaltitle | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
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dc.description.tc | 19 | - |
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