RGD Reference Report - Retinoids induce MMP-9 expression through RARalpha during mammary gland remodeling. - Rat Genome Database

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Retinoids induce MMP-9 expression through RARalpha during mammary gland remodeling.

Authors: Zaragoza, R  Gimeno, A  Miralles, VJ  Garcia-Trevijano, ER  Carmena, R  Garcia, C  Mata, M  Puertes, IR  Torres, L  Vina, JR 
Citation: Zaragoza R, etal., Am J Physiol Endocrinol Metab. 2007 Apr;292(4):E1140-8. Epub 2006 Dec 12.
RGD ID: 1642048
Pubmed: PMID:17164434   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00463.2006   (Journal Full-text)

Retinoic acid (RA) is a signaling molecule in the morphogenesis of the mammary gland, modulating the expression of matrix metalloproteinases (MMPs). The aim of this paper was to study the role of RA during weaning, which consists of three events: apoptosis of the secretory cells, degradation of the extracellular matrix, and adipogenesis. CRABP II and CRBP-1 carrier proteins increased significantly during weaning compared with lactating glands but reverted to control values after the litter resuckled. The effects of RA are mediated by the nuclear receptors RARalpha, RARbeta, RARgamma, and RXRalpha, which underwent an increase in protein levels during weaning. In an attempt to elucidate the RARalpha-dependent signaling pathway, ChIP assays were performed. The results showed the binding of RARalpha to the MMP-9 promoter after 24- and 72-h weaning together with its coactivator p300; this fact could be responsible for the increase found in MMP-9 mRNA and protein levels in these conditions. Expression of related MMPs (MMP-2 and MMP-3) was also increased during weaning. Using gelatine zymography, we observed a time-dependent increase in active forms of MMP-9 and MMP-2. On the other hand, the inhibitor of MMPs, TIMP-1, was almost undetectable at 24- and 72-h weaning by Western blot. The role of retinoids in matrix remodeling is reinforced by the fact that administration of an acute dose of retinol palmitate to control lactating rats also induces MMP-9 expression. This emphasizes the importance of retinoids in vivo to regulate mammary gland involution.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ep300Ratresponse to retinoic acid  IEP  RGD 
Mmp9Ratresponse to vitamin A  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ep300  (E1A binding protein p300)
Mmp9  (matrix metallopeptidase 9)


Additional Information