Modulation of PDGF-C and PDGF-D expression during bleomycin-induced lung fibrosis.
PDGF isoforms are a family of polypeptides that bind to cell surface receptors and induce fibroblast proliferation and chemotaxis. The PDGF-A and -B chain isoforms have been implicated in fibroproliferative lung injury in animal models and in human disease. Two recently recognized PDGF polypeptides, PDGF-C and -D, differ from the PDGF-A and -B isoforms in that they require proteolytic cleavage before they can bind and activate the PDGF receptors. Our findings demonstrate that administration of bleomycin to murine lungs leads to a significant increase in PDGF-C mRNA expression and a significant decrease in PDGF-D mRNA expression. PDGF-C expression was localized to areas of lung injury by in situ hybridization, and PDGF-C expression was not upregulated in the lungs of BALB/c mice that are resistant to bleomycin-induced lung fibrosis. Moreover, there is in vivo phosphorylation of the PDGF-receptor that binds PDGF-C in response to bleomycin administration. These observations strongly suggest a role for PDGF-C in bleomycin-induced pulmonary fibrosis.
Zhuo
Ying
Y
Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Ave., New Orleans, LA 70112, USA.
Zhang
Jian
J
Laboy
Miguel
M
Lasky
Joseph A
JA
D000818:Animals; D000964:Antimetabolites, Antineoplastic; D001761:Bleomycin; D015870:Gene Expression; D008222:Lymphokines; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D008222:Lymphokines; C498951:Pdgfd protein, mouse; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C411423:platelet-derived growth factor C; D001761:Bleomycin; D017479:Receptors, Platelet-Derived Growth Factor