An Autocrine/Paracrine Role of Human Decidual Relaxin. I. Interstitial Collagenase (Matrix Metalloproteinase-1) and Tissue Plasminogen Activator1

Abstract

Decidual and placental relaxins have been proposed as autocrine/ paracrine hormones in the remodeling of collagen in the amnion and chorion in the last weeks of pregnancy. The matrix metalloproteinase-1 (MMP-1) is a key enzyme in the degradation of the interstitial collagens which predominate in the fetal membranes. Distribution of the MMP-1 gene and of the MMP-1 protein was shown by in situ hybridization and immunolocalization, respectively, in amnion, chorion, and decidua collected from patients before the onset of spontaneous labor. The distribution of MMP-1 in the chorionic cytotrophoblast and decidua coincided with that of the human relaxin receptor, detected by tissue section autoradiography in tissues collected at the same stage of pregnancy. Fetal membrane explants were used to study the effect of exogenous human relaxin H2. These responded by a dose-dependent increase in expression of the MMP-1 gene, in its secreted protein, and in its enzyme activity in the medium. A similar dose-dependent increase in the tissue plasminogen activator (tPA) gene and protein upon exposure of the explants to relaxin H2 suggested a coordinated cascade system, resulting in increases in secreted activities of MMP-1, MMP-3 (stromelysin), and MMP-9 (gelatinase B). There was no effect on the genes or proteins for MMP-2 (gelatinase A) or tissue inhibitor of metalloproteinase-1 (TIMP-1), showing the specificity of the response. This coordinated regulation by relaxin H2 of tPA, MMP-1, MMP-3, and MMP-9 would result in more complete degradation of the fetal membrane extracellular matrix components.

Yeast Nuclear Extract Contains Two Major Forms of RNA Polymerase II Mediator Complexes

“…Nevertheless, the possibility that Mcol-A and Mcol-B are involved in other processes distinct from blastocyst invasion, including angiogenesis regulation or collagen turnover accompanying decidualization, cannot be ruled out. It is also noteworthy in the context of the putative relationships between these novel murine MMPs and human MMP-1, that this interstitial collagenase has been also found to be produced by trophoblastic cells during human pregnancy (43,44). These data suggest that the parallelisms between human MMP-1, and murine Mcol-A and Mcol-B, could be extended to their respective expression patterns.…”

Relaxin Enhances the Collagenolytic Activity and In Vitro Invasiveness by Upregulating Matrix Metalloproteinases in Human Thyroid Carcinoma Cells

“…In the human thyroid gland, RLN2 is exclusively detected in thyroid cancer tissues and enhances the production and secretion of the lysosomal acid hydrolases of the cathepsin family which promote penetration of elastin matrices by human thyroid cancer cells (7). Earlier reports supported a role for RLN in ECM remodeling by upregulating cathepsin B and dipeptidyl peptidase I in the mouse pubic symphysis and urokinase and tissue type plasminogen activator in the uterus and cervix of prepubertal gilts (22)(23)(24). Members of the family of matrix metalloproteinases (MMP) and their tissue inhibitors of MMP (TIMP1-4) are another group of proteinases responsive to RLN.…”

“…RLN affects the expression and/or secretion of collagenase 1 (MMP1) and 3 (MMP13), gelatinase A (MMP2) and B (MMP9), stromelysin1 (MMP3), and MT1-MMP in the periodontal apparatus and joints (38)(39)(40), lung (13), reproductive tissues (24,(41)(42)(43), human renal fibroblasts (44), and human breast cancer cells (20). We previously showed that human thyroid cancer tissue is a source of RLN2 and that RLN2 enhances elastin matrix degradation by thyroid cancer cells (7).…”

Lack of an Association of a Single Nucleotide Polymorphism in the Promoter of the Matrix Metalloproteinase-1 Gene in Czech Women with Pregnancy-Induced Hypertension

“…Interstitial collagenase (MMP1) degrades collagens I, II, III, VII and X, the most abundant compounds of the connective tissue [9]. MMP1 is released by decidual, endothelial and trophoblast cells [10][11][12]. In cell culture, endothelial cells isolated from the decidual arteries of preeclamptic placentas produced smaller amounts of MMP1 than endothelia from normal decidua, and the MMP1 to tissue inhibitor of metalloproteinase-1 (TIMP-1) production ratio was low too.…”