Diet-induced obesity and reduced skin cancer susceptibility in matrix metalloproteinase 19-deficient mice.
Matrix metalloproteinase 19 (MMP-19) is a member of the MMP family of endopeptidases that, in contrast to most MMPs, is widely expressed in human tissues under normal quiescent conditions. MMP-19 has been found to be associated with ovulation and angiogenic processes and is deregulated in diverse pathological conditions such as rheumatoid arthritis and cancer. To gain further insights into the in vivo functions of this protease, we have generated mutant mice deficient in Mmp19. These mice are viable and fertile and do not display any obvious abnormalities. However, Mmp19-null mice develop a diet-induced obesity due to adipocyte hypertrophy and exhibit decreased susceptibility to skin tumors induced by chemical carcinogens. Based on these results, we suggest that this enzyme plays an in vivo role in some of the tissue remodeling events associated with adipogenesis, as well as in pathological processes such as tumor progression.
Pendás
Alberto M
AM
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Spain. amp@correo.uniovi.es
Folgueras
Alicia R
AR
Llano
Elena
E
Caterina
John
J
Frerard
Françoise
F
Rodríguez
Francisco
F
Astudillo
Aurora
A
Noël
Agnès
A
Birkedal-Hansen
Henning
H
López-Otín
Carlos
C
D017667:Adipocytes / Q000201:enzymology / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity; D048429:Cell Size; D018076:DNA, Complementary / Q000235:genetics; D004032:Diet; D005260:Female; D018390:Gene Targeting; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D009765:Obesity / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*
D002273:Carcinogens; D018076:DNA, Complementary; D008748:Methylcholanthrene; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19