In:
Blood, American Society of Hematology, Vol. 108, No. 6 ( 2006-09-15), p. 1821-1829
Abstract:
Brief treatment with transforming growth factor (TGF)–β1 stimulated the migration of macrophages, whereas long-term exposure decreased their migration. Cell migration stimulated by TGF-β1 was markedly inhibited by 10 μg/mL Tat-C3 exoenzyme. TGF-β1 increased mRNA and protein levels of macrophage inflammatory protein (MIP)–1α in the initial period, and these effects also were inhibited by 10 μg/mL Tat-C3 and a dominant-negative (DN)–RhoA (N19RhoA). Cycloheximide, actinomycin D, and antibodies against MIP-1α and monocyte chemoattractant protein-1 (MCP-1) abolished the stimulation of cell migration by TGF-β1. These findings suggest that migration of these cells is regulated directly and indirectly via the expression of chemokines such as MIP-1α and MCP-1 mediated by RhoA in response to TGF-β1. TGF-β1 activated RhoA in the initial period, and thereafter inactivated them, suggesting that the inactivation of RhoA may be the cause of the reduced cell migration in response to TGF-β1 at later times. We therefore attempted to elucidate the molecular mechanism of the inactivation of RhoA by TGF-β1. First, TGF-β1 phosphorylated RhoA via protein kinase A, leading to inactivation of RhoA. Second, wild-type p190 Rho GTPase activating protein (p190RhoGAP) reduced and DN-p190RhoGAP reversed the reduction of cell migration induced by TGF-β, suggesting that it inactivated RhoA via p190 Rho GAP.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2005-10-009191
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2006
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
