HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Papers In Press, published online ahead of print December 1, 2003
J. Lipid Res., doi:10.1194/jlr.M300266-JLR200

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: M300266-JLR200v1 44/12/2382    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dobreva, I. Articles by Widmann, C. Search for Related Content PubMed PubMed Citation Articles by Dobreva, I. Articles by Widmann, C. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 44, 2382-2390, December 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

LDLs induce fibroblast spreading independently of the LDL receptor via activation of the p38 MAPK pathway

Iveta Dobreva^*, Gérard Waeber, Vincent Mooser, Richard W. James^1, and Christian Widmann^1,2,*

^* Institut de Biologie Cellulaire et de Morphologie, Université de Lausanne, Switzerland
Département de Médecine Interne, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Lipid Laboratory, Clinical Diabetes Unit, University Hospital, Geneva, Switzerland

² To whom correspondence should be addressed. e-mail: christian.widmann{at}ibcm.unil.ch

Because adventitial fibroblasts play an important role in the repair of blood vessels, we assessed whether elevation in LDL concentrations would affect fibroblast function and whether this depended on activation of intracellular signaling pathways. We show here that in primary human fibroblasts, LDLs induced transient activation of the p38 mitogen-activated protein kinase (MAPK) pathway, but not the c-Jun N-terminal kinase MAPK pathway. This activation did not require the recruitment of the LDL receptor (LDLR), because LDLs efficiently stimulated the p38 MAPK pathway in human and mouse fibroblasts lacking functional LDLR, and because receptor-associated protein, an LDLR family antagonist, did not block the LDL-induced p38 activation. LDL particles also induced lamellipodia formation and cell spreading. These effects were blocked by SB203580, a specific p38 inhibitor.

Our data demonstrate that LDLs can regulate the shape of fibroblasts in a p38 MAPK-dependent manner, a mechanism that may participate in wound healing or vessel remodeling as in atherosclerosis.

Abbreviations: FACS, fluorescent-activated cell sorter; FCS, fetal calf serum; FH, familial hypercholesterolemia; HS, human serum; JNK, c-Jun N-terminal kinase; LDLR, LDL receptor; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MEF, mouse embryonic fibroblast; RAP, receptor-associated protein; SAPK, stress-activated protein kinase; SREBP, sterol-regulatory element binding protein

Supplementary key words remodeling • cell spreading • lamellipodia • p38 mitogen-activated protein kinase • low density lipoprotein • lipoproteins • low density lipoprotein receptor • fibroblasts

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Bulat, G. Waeber, and C. Widmann LDLs stimulate p38 MAPKs and wound healing through SR-BI independently of Ras and PI3 kinase J. Lipid Res., January 1, 2009; 50(1): 81 - 89. [Abstract] [Full Text] [PDF]

				I. Dobreva, G. Waeber, R. W. James, and C. Widmann Interleukin-8 Secretion by Fibroblasts Induced by Low Density Lipoproteins Is p38 MAPK-dependent and Leads to Cell Spreading and Wound Closure J. Biol. Chem., January 6, 2006; 281(1): 199 - 205. [Abstract] [Full Text] [PDF]