Substance P up-regulates matrix metalloproteinase-1 and down-regulates collagen in human lung fibroblast.
Substance P is involved in inflammatory processes, but its effect on extracellular matrix metabolism has not been studied; therefore, the authors evaluated its effect on collagen synthesis and degradation, expression of pro-alpha1(I) collagen, matrix metalloproteinase-1 and -2, and tissue inhibitor of metalloproteinase-1 and -2 in normal human lung fibroblast strains. Substance P induced a decrease in collagen biosynthesis, concomitant to a down-regulation of pro-alpha1(I) collagen mRNA. In contrast, an increase in collagen degradation was observed, accompanied with an up-regulation of matrix metalloproteinase-1. Substance P did not influence tissue inhibitor of metalloproteinase-1 and -2 or matrix metalloproteinase-2 expression. The results suggest that substance P participates in extracellular matrix metabolism.
Ramos
Carlos
C
Departamento de Fibrosis Pulmonar, Instituto Nacional de Enfermedades Respiratorias, México, DF, México. mamora572002@yahoo.com.mx
Montaño
Martha
M
Cisneros
Jose
J
Sommer
Bettina
B
Delgado
Javier
J
Gonzalez-Avila
Georgina
G
D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D002675:Child, Preschool; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004790:Enzyme Induction; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D064729:Neurokinin-1 Receptor Antagonists; D012333:RNA, Messenger / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
D024042:Collagen Type I; D064729:Neurokinin-1 Receptor Antagonists; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D013373:Substance P; D014364:Tryptophan; D003094:Collagen; D020781:Matrix Metalloproteinase 1