Matrix Metalloproteinase Expression and Activity Following Prostaglandin F2α-Induced Luteolysis1

Abstract

Luteal tissue contains matrix metalloproteinases (MMPs) that cleave specific components of the extracellular matrix (ECM) and are inhibited by tissue inhibitors of metalloproteinases (TIMPs). We previously reported a decrease in luteal TIMP-1 within 15 min of prostaglandin F(2 alpha) (PGF(2 alpha))-induced luteolysis. An increase in the MMP:TIMP ratio may promote ECM degradation and apoptosis, as observed in other tissues that undergo involution. The objectives of these experiments were to determine whether 1) PGF(2 alpha) affects expression of mRNA encoding fibrillar collagenases (MMP-1 and -13), gelatinases A and B (MMP-2 and -9), membrane type (mt)-1 MMP (MMP-14), stromelysin (MMP-3), and matrilysin (MMP-7), and 2) PGF(2 alpha) increases MMP activity during PGF(2 alpha)-induced luteolysis in sheep. Corpora lutea (n = 3-10/time point) were collected at 0, 15, and 30 min and 1, 2, 4, 6, 12, 24, and 48 h after PGF(2 alpha) administration. Northern blot analysis confirmed the presence of all MMPs except MMP-9. Expression of mRNA for the above MMPs (except MMP-2) increased significantly (P < 0.05) by 30 min, and all MMPs increased significantly (P < 0.05) by 6 h after PGF(2 alpha) administration. Expression of MMP-14 mRNA increased significantly (P < 0.05) by 15 min post-PGF(2 alpha) and remained elevated through 48 h. MMP activity in luteal homogenates (following proenzyme activation and inactivation of inhibitors) was increased significantly (P < 0.05) by 15 min and remained elevated through 48 h post-PGF(2 alpha). MMP activity was localized (in situ zymography) to the pericellular area of various cell types in the 0-h group and was markedly increased by 30 min post-PGF(2 alpha). MMP mRNA expression and activity were significantly increased following PGF(2 alpha) treatment. Increased MMP activity may promote ECM degradation during luteolysis.

Chemical Modification of Interleukin-10 with Mannose 6-Phosphate Groups Yields a Liver-Selective Cytokine

“…Under conditions in which TIMP-1 levels are increased and MMP13 levels are decreased, there is an increased deposition of fibrillar collagens in the liver. The imbalance between MMP-13 and TIMP-1 can be expressed as the MMP-13/TIMP-1 ratio (Vaillant et al, 2001;Ricke et al, 2002). In this study, we observed antifibrotic effects of both IL10 and M6P-IL10 via the regulation of MMP-13 and TIMP-1 mRNA expressions.…”

“…In vivo, the ratio between matrix-degrading activity and inhibition of this activity determines the net outcome of the process. When the ratio of MMP-13 and TIMP-1 was determined (Vaillant et al, 2001;Ricke et al, 2002), we assessed that IL10 and M6PIL-10 both significantly enhanced this ratio (Fig. 4).…”

Expression and Regulation of MMP1, MMP3, and MMP9 in the Chicken Ovary in Response to Gonadotropins, Sex Hormones, and TGFB11

“…In addition, MMP3 mRNA was detected in ovine CL and was transiently increased within 30 min of functional luteal regression [40]. We found that, in chicken, MMP3 expression gradually increased with follicular maturation and reached its highest level in F1 follicles.…”

“…A rapid decrease in the MMP3 ZHU ET AL. mRNA was observed in chicken POF follicles, which is in contrast with MMP3 induction during ovine luteolysis [40]. The temporal MMP3 expression pattern indicates that it is probably involved in chicken ovulation but not POF regression.…”

Insights into the Activity, Differential Expression, Mutual Regulation, and Functions of Matrix Metalloproteinases and A Disintegrin and Metalloproteinases in Hypertension and Cardiac Disease

“…Recent reports describe intriguing relationships between metalloproteinases and lipids that are mediated by transcription factors (such as PPARs), lipid carrier proteins (such as apolipoproteins), and lipoparticle receptors (such as LRP-1). GPCRs are among the receptors for lipids and lipids are among the transactivators of metalloproteinases and signaling of the EGFR pathway [149,156,157]. In addition, the GTPases Rho, Rac and Ras, which are associated with the transduction of growth signals from GPCRs, require isoprenylation for their activity [158].…”