First Author | Ahmad N | Year | 2012 |
Journal | Mol Cell Endocrinol | Volume | 363 |
Issue | 1-2 | Pages | 46-61 |
PubMed ID | 22835547 | Mgi Jnum | J:189583 |
Mgi Id | MGI:5446529 | Doi | 10.1016/j.mce.2012.07.006 |
Citation | Ahmad N, et al. (2012) Relaxin induces matrix-metalloproteinases-9 and -13 via RXFP1: induction of MMP-9 involves the PI3K, ERK, Akt and PKC-zeta pathways. Mol Cell Endocrinol 363(1-2):46-61 |
abstractText | 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-zeta and the transcription factors Elk-1, c-fos and, to a lesser extent, NF-kappaB 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. |