View : 79 Download: 0

RhoA-mediated signaling up-regulates hepatocyte growth factor gene and protein expression in response to apoptotic cells

Title
RhoA-mediated signaling up-regulates hepatocyte growth factor gene and protein expression in response to apoptotic cells
Authors
Park H.-J.Choi Y.-H.Cho Y.J.Henson P.M.Kang J.L.
Ewha Authors
이지희조영주최윤희
SCOPUS Author ID
이지희scopus; 조영주scopus; 최윤희scopus
Issue Date
2011
Journal Title
Journal of Leukocyte Biology
ISSN
0741-5400JCR Link
Citation
vol. 89, no. 3, pp. 399 - 411
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Clearance of apoptotic cells by macrophages induces HGF secretion. We examined the regulatory mechanisms of HGF mRNA and protein expression in macrophages upon exposure to apoptotic cells. The interaction of RAW 264.7 macrophages with apoptotic Jurkat cells, but not with viable cells, resulted in expression of HGF mRNA and protein. Exposure of RAW 264.7 cells to apoptotic cells induced activation of RhoA, the PI3K/Akt pathway, and MAPKs, including p38 MAPK, ERK, and JNK. Down-regulation of the RhoA/Rho kinase pathway by pharmacological inhibitors or a RhoA-specific siRNA suppressed HGF mRNA and protein expression by macrophages in response to apoptotic cells through the phosphorylation of Akt and the MAPKs. Inhibition of PI3K decreased phosphorylation of Akt and the MAPKs. Inhibition of JNK, but not p38 MAPK and ERK, reduced Akt phosphorylation. The pharmacological inhibitor of PI3K and the MAPKs blocked HGF mRNA and protein expression. Other types of apoptotic cells, such as HeLa cells and murine thymocytes, could also induce HGF mRNA through the RhoA-dependent pathway. Likely, the RhoA-dependent signaling pathway was required for HGF mRNA induction in primary cells of peritoneal macrophages in response to apoptotic cells. An HGFR-blocking antibody did not alter apoptotic cell-induced activation of RhoA, Akt, and the MAPKs, as well as HGF production. Overall, the data provide evidence that activation of the RhoA/Rho kinase pathway up-regulates transcriptional HGF production in response to apoptotic cells. © Society for Leukocyte Biology.
DOI
10.1189/jlb.0710414
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE