2011 Fiscal Year Final Research Report
The effect of hepatocyte growth factor(HGF) on the blood-brain barrier
| Project/Area Number |
22791759
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Emergency medicine
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| Research Institution | 独立行政法人国立病院機構長崎医療センター臨床研究センター (2011)
Department of Clinical Research, National Hospital Organization Nagasaki Medical Center (2010) |
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Principal Investigator |
YAMADA Narumi 独立行政法人国立病院機構長崎医療センター臨床研究センター, 救命救急, 医師 (30463532)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 血液脳関門(BBB) / 肝細胞増殖因子(HGF) / tight junction / adherens junction / TEER / 透過性 |
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| Research Abstract |
Immunofluorescent staining, western blot analysis and RT-PCR indicated that rat brain microvascular endothelial cells(RBECs) expressed c-Met as the HGF receptor.
The effect of HGF on barrier function was investigated using an in vitro model of the blood-brain barrier(BBB) with a primary culture of RBECs. HGF decreased permeability to sodium fluorescein and Evans blue albumin through the RBECs monolayer, and dose-dependently increased transendothelial electrical resistance(TEER). It was thought that HGF had a protective effect on BBB function by initially targeting the TJ. However, immunofluorescent staining and Western blot analysis indicated that HGF treatment did not significantly change the tight junction proteins claudin-3, claudin-5, occludin and ZO-1 in RBECs. In comparison, E-cadherin as adherens junction protein was increased by HGF treatment. HGF reduced cortical actin bands and increased stress fiber density in F-actin bands. HGF altered immunohistochemical staining pattern of F-actin bands. HGF seems to act on the BBB to strengthen BBB integrity, but the mechanism was not caused by changes of tight junction proteins. Other mechanisms, for example, cytoskeletal rearrangement could be a candidate mechanism for the effect of HGF on BBB.
Furthermore, in the tight junctional function of BBB in RBECs, it was indicated that Transforming growth factor-beta(TGF-β) had opposite effects from HGF.
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