title: Curcumin delays endometriosis development by inhibiting MMP-2 activity.
abstract: Endometriosis is a common reproductive disorder believed to be associated with matrix metalloproteinases (MMPs) activities for invasion and remodeling of endometrial tissues. Ectopic endometrium has higher capacity to produce proMMP-2 than eutopic tissues; however, the role of MMP-2 during early phase of endometriosis development is still unclear. In the present study, we investigated the role of MMP-2 in establishment and development of endometriosis in mouse model. The effect of curcumin on regression of endometriosis through protease/antiprotease balance between MMP-2 and TIMP-2 was also examined. After endometrial inoculation into peritoneum, we observed a significant elevation of proMMP-2 activity from day 2 onwards. This increased MMP-2 activity was associated with decreased expression of tissue inhibitor of MMP (TIMP)-2, while a significant up-regulation of active MMP-2 activity was observed from day 3 onwards. The activation of proMMP-2 to active MMP-2 was associated with increased expression of membrane type 1 matrix metalloproteinase (MT1MMP). Curcumin at a dose of 48 mg/kg b.w. repressed the MMP-2 activity via up-regulation of bound TIMP-2 expression, thus delayed endometriosis development. In addition, curcumin inhibited production of active MMP-2 by down-regulating MT1MMP expression. Moreover, endometriotic progression was directly linked with increased MMP-2/TIMP-2 ratio which was delayed by curcumin pretreatment. In summary, our study documents the regulation of MMP-2 activity by TIMP-2 during the early phase of endometriosis development and inhibitory action of curcumin thereon.
authors.affiliation: Department of Physiology, Drug Development Diagnostics & Biotechnology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Sayantan
authors.initials: S
authors.lastname: Jana
authors.forename: Deep Sankar
authors.initials: DS
authors.lastname: Rudra
authors.forename: Sumit
authors.initials: S
authors.lastname: Paul
authors.forename: Swarnakar
authors.initials: S
authors.lastname: Snehasikta
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003474:Curcumin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000201:enzymology* / Q000517:prevention & control*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D010532:Peritoneal Diseases / Q000201:enzymology* / Q000517:prevention & control*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D061965:Matrix Metalloproteinase Inhibitors; D020778:Matrix Metalloproteinase 2; D003474:Curcumin