PMID- 18566004
OWN - NLM
STAT- MEDLINE
DCOM- 20081117
LR  - 20220321
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 586
IP  - 16
DP  - 2008 Aug 15
TI  - CC family chemokines directly regulate myoblast responses to skeletal muscle 
      injury.
PG  - 3991-4004
LID - 10.1113/jphysiol.2008.152090 [doi]
AB  - Chemokines have been implicated in the promotion of leucocyte trafficking to 
      diseased muscle. The purpose of this study was to determine whether a subset of 
      inflammatory chemokines are able to directly drive myoblast proliferation, an 
      essential early component of muscle regeneration, in a manner which is entirely 
      independent of leucocytes. Cultured myoblasts (C2C12) were exposed to monocyte 
      chemoattractant protein-1 (MCP-1; CCL2), macrophage inflammatory protein-1alpha 
      (MIP-1alpha; CCL3) or MIP-1beta (CCL4). All chemokines induced phosphorylation of 
      extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinase 
      (MAPK) and greatly increased myoblast proliferative responses. Chemokine-induced 
      myoblast proliferation was abolished by pertussis toxin and the MEK1/2 inhibitor 
      U0126, implicating both Galphai-coupled receptors and ERK1/2-dependent 
      signalling. Myoblasts expressed receptors for all of the chemokines tested, and 
      mitogenic responses were specifically inhibited by antibodies directed against CC 
      family chemokine receptors 2 and 5 (CCR2 and CCR5). Within an in vitro myogenic 
      wound healing assay devoid of leucocytes, all chemokines significantly 
      accelerated the time course of myoblast wound closure after mechanical injury. 
      Injections of MCP-1 into cardiotoxin-injured skeletal muscles in vivo also 
      suppressed expression of the differentiation marker myogenin, consistent with a 
      mitogenic effect. Taken together, our results indicate that CC chemokines have 
      potent and direct effects on myoblast behaviour, thus indicating a novel role in 
      muscle repair beyond leucocyte chemoattraction. Therefore, interventions aimed at 
      modulating the balance between myoblast and leucocyte effects of CC chemokines in 
      injured muscle could represent a novel strategy for the treatment of destructive 
      muscle pathologies.
FAU - Yahiaoui, Linda
AU  - Yahiaoui L
AD  - Meakins-Christie Laboratories, McGill University, 3626 St Urbain Street, 
      Montreal, Quebec, Canada H2X 2P2.
FAU - Gvozdic, Dusanka
AU  - Gvozdic D
FAU - Danialou, Gawiyou
AU  - Danialou G
FAU - Mack, Matthias
AU  - Mack M
FAU - Petrof, Basil J
AU  - Petrof BJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080619
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Chemokines, CC)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chemokines, CC/*metabolism
MH  - Mice
MH  - Muscle, Skeletal/*injuries/*metabolism/pathology
MH  - Myoblasts/*metabolism/pathology
PMC - PMC2538927
EDAT- 2008/06/21 09:00
MHDA- 2008/11/18 09:00
PMCR- 2009/08/15
CRDT- 2008/06/21 09:00
PHST- 2008/06/21 09:00 [pubmed]
PHST- 2008/11/18 09:00 [medline]
PHST- 2008/06/21 09:00 [entrez]
PHST- 2009/08/15 00:00 [pmc-release]
AID - jphysiol.2008.152090 [pii]
AID - 10.1113/jphysiol.2008.152090 [doi]
PST - ppublish
SO  - J Physiol. 2008 Aug 15;586(16):3991-4004. doi: 10.1113/jphysiol.2008.152090. Epub 
      2008 Jun 19.