Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relaxin promotes softening of the uterine cervix and inhibits uterine contractility in rats, mice and pigs. Little information, however, is available about the role of relaxin in humans. In 2002, LGR7 and LGR8 were discovered to be receptors for relaxin and those receptors were identified in the human placenta. Thus, in this study, effects of recombinant H2 (rH2) relaxin on human early placental extravillous trophoblasts (EVTs) were examined. Isolation of EVTs from early placental trophoblasts was performed using the procedures established in our laboratory. After 48-h subculture, the presence of relaxin receptors in cultured EVTs was characterized by RT-PCR and immunoblotting. The cultured EVTs were treated with different doses (0.3-3 ng/ml) of rH2 relaxin for 24 h. The effects of rH2 relaxin on MMP-2, -3, -9 and TIMP-1 mRNAs levels were examined by real-time RT-PCR. RT-PCR and immunoblotting revealed that relaxin receptors are present in early placental EVTs. Treatment with rH2 relaxin increased MMP-2 and -9 mRNAs levels and decreased TIMP-1 mRNA levels in cultured EVTs, whereas rH2 relaxin did not affect MMP-3 mRNA levels. These results suggest that relaxin may promote the invasive potential of early placental EVTs through up-regulating MMP-2, -9 mRNAs and down-regulating TIMP-1 mRNA in EVTs.
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PMID:Effects of recombinant H2 relaxin on the expression of matrix metalloproteinases and tissue inhibitor metalloproteinase in cultured early placental extravillous trophoblasts. 1823 74

Our long-term goal is to understand the mechanisms by which relaxin and estrogen potentially contribute to joint diseases, particularly those afflicting the fibrocartilaginous temporomandibular joint (TMJ). Previously, we showed that relaxin produces a dose-dependent induction of tissue-degrading enzymes of the matrix metalloproteinase (MMP) family, specifically MMP-1 (collagenase-1), MMP-3 (stromelysin-1), MMP-9 (92-kDa gelatinase), and MMP-13 (collagenase-3) in cell isolates and tissue explants from TMJ fibrocartilage. The induction of these MMPs is accompanied by loss of collagen and glycosaminoglycans (GAGs), which was blocked by a pan-MMP inhibitor. We also found the targeted in vivo loss of collagen and GAGs in TMJ discs of ovariectomized rabbits treated with beta-estradiol, relaxin, or both hormones together. Progesterone attenuated the induction of MMPs and matrix loss by relaxin and estrogen. The modulation of matrix composition in TMJ fibrocartilage by these hormones was similar to that observed in the pubic symphysis and differed from that of the knee meniscus. The two target tissues showing the greatest modulation of MMPs and matrix loss, namely, the TMJ disc and pubic symphysis, had similar expression profiles of the estrogen receptors alpha and beta, relaxin-1 receptor (RXFP1, LGR7), and insulin-like peptide 3 receptor (RXFP2, LGR8) and these profiles differed from those in cells from the knee meniscus. These findings suggest a novel model for targeted tissue turnover of cartilage of specific joints through hormone-mediated induction of select MMPs.
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PMID:Matrix metalloproteinase induction by relaxin causes cartilage matrix degradation in target synovial joints. 1941 13