title: Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases.
abstract: The invasion cascade exhibited by placental trophoblasts and cancerous cells bears many similarities, and it is attributed to extracellular matrix degradation mediated by matrix metalloproteinases (MMPs). Although proper and controlled invasion by trophoblasts into the maternal uterus is an essential requirement for maintenance of normal pregnancy, any abnormality in this phenomenon results in the development of invasion-related disorders such as gestational trophoblastic diseases (GTDs) and preeclampsia. We studied the epigenetic basis of differential expression of two placental MMPs (MMP2 and MMP9) and tissue inhibitors of metalloproteinases (TIMP2 and TIMP1) during normal gestation and invasion-related disorders, i.e., preeclampsia and GTDs. Our study suggests the association of H3K9/27me3 with differential expression of these MMPs and their inhibitors, which regulate the placental invasion during normal pregnancy, whereas no role of CpG methylation was observed in the differential expression of MMPs/TIMPs. Further, development of GTDs was associated with abnormally higher expression of these MMPs and lower levels of their inhibitors, whereas the reverse trends were observed for MMPs and their TIMPs in case of preeclampsia, in association with abnormal changes in H3K9/27me3. These results suggest the involvement of higher levels of MMPs in an aggressive invasive behavior depicted by GTDs, whereas lower levels of these MMPs in shallow and poor invasive phenotype associated with preeclampsia. Thus, our study shows the significance of a proper balance regulated by histone trimethylation between differential expression of MMPs and their TIMPs for maintaining normal pregnancy and its deregulation as a contributing factor for pathogenesis of invasive disorders during pregnancy.
authors.affiliation: Department of BiochemistryPostgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Beenish
authors.initials: B
authors.lastname: Rahat
authors.affiliation: Department of BiochemistryPostgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Obstetrics and GynecologyPostgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Bagga
authors.affiliation: Cancer Pharmacology DivisionCSIR-Indian Institute of Integrative Medicine, Jammu, India.
authors.forename: Abid
authors.initials: A
authors.lastname: Hamid
authors.affiliation: Department of BiochemistryPostgraduate Institute of Medical Education and Research, Chandigarh, India jyotdeep2001@yahoo.co.in.
authors.forename: Jyotdeep
authors.initials: J
authors.lastname: Kaur
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D019175:DNA Methylation; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology
chemical_list: C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9