title: Relaxin induces matrix-metalloproteinases-9 and -13 via RXFP1: induction of MMP-9 involves the PI3K, ERK, Akt and PKC-ζ pathways.
abstract: We determined the precise role of relaxin family peptide (RXFP) receptors-1 and -2 in the regulation of MMP-9 and -13 by relaxin, and delineated the signaling cascade that contributes to relaxin's modulation of MMP-9 in fibrocartilaginous cells. Relaxin treatment of cells in which RXFP1 was silenced resulted in diminished induction of MMP-9 and -13 by relaxin, whereas overexpression of RXFP1 potentiated the relaxin-induced expression of these proteinases. Suppression or overexpression of RXFP2 resulted in no changes in the relaxin-induced MMP-9 and -13. Studies using chemical inhibitors and siRNAs to signaling molecules showed that PI3K, Akt, ERK and PKC-ζ and the transcription factors Elk-1, c-fos and, to a lesser extent, NF-κB are involved in relaxin's induction of MMP-9. Our findings provide the first characterization of signaling cascade involved in the regulation of any MMP by relaxin and offer mechanistic insights on how relaxin likely mediates extracellular matrix turnover.
authors: The University of Michigan, Ann Arbor, MI 48109-1078, USA.
authors: Nisar
authors: N
authors: Ahmad
authors: Wei
authors: W
authors: Wang
authors: Remi
authors: R
authors: Nair
authors: Sunil
authors: S
authors: Kapila
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051445:Fibrocartilage / Q000166:cytology; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012065:Relaxin / Q000502:physiology*; D015398:Signal Transduction; D015533:Transcriptional Activation; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism; D000099221:Protein Kinase C zeta
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D053509:Matrix Metalloproteinase 13; D053511:Matrix Metalloproteinase 14; D020780:Matrix Metalloproteinase 9; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D012065:Relaxin; D050807:ets-Domain Protein Elk-1; D000099221:Protein Kinase C zeta; C494113:Elk1 protein, mouse; C507096:Mmp14 protein, mouse; C478103:RXFP1 protein, mouse; C514862:Akt1 protein, mouse; C507081:Mmp13 protein, mouse; C501830:Mmp9 protein, mouse