Cutting edge: proliferating fibroblasts respond to collagenous C1q with phosphorylation of p38 mitogen-activated protein kinase and apoptotic features.
Interactions of C1q collagen tails with human fibroblasts induce G(1) mitotic arrest. The hypothesis tested in this study is that the antiproliferative effect of C1q tails is mediated through activation of stress responsive pathway(s). Upon C1q treatment, proliferating fibroblasts were examined by immunoblotting with a panel of Abs to the mitogen-activated protein kinase (MAPK) superfamily. The cells selectively increased phosphorylation of p38 MAPK, upstream dual activator MAPK kinase 3/6, and downstream transcription factors activating transcription factor 2, ETS domain transcription factor 1, and C/EBP homologous protein in a time-dependent manner. Phosphorylations were mediated, in part, by ligation of surface C1q tail-binding calreticulin. These events correlated with the appearance of apoptotic nuclei and DNA fragmentation in the cultures, which increased with a time response curve. The apoptotic features were linked to p38 activities because the selective inhibitor SB203580 prevented both phosphorylation of the pathway and DNA fragmentation. Hence, p38 activation might provide a molecular basis for linking mitotic arrest and apoptosis of fibroblasts by C1q tails.
Bordin
Sandra
S
Department of Periodontics, University of Washington, Seattle 98195, USA. bordin@u.washington.edu
Whitfield
Douglas
D
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology*; D015922:Complement C1q / Q000037:antagonists & inhibitors / Q000502:physiology*; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D003169:Complement Inactivator Proteins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D015922:Complement C1q; D003094:Collagen; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580