Curcumin delays endometriosis development by inhibiting MMP-2 activity.

Sayantan Jana, Jana S, Deep Sankar Rudra, Paul S, Sumit Paul, Swarnakar Snehasikta, Snehasikta S, Snehasikta Swarnakar
Indian journal of biochemistry & biophysics · 2012 · vol. 49(5) , pp. 342–8 · PMID:23259320 · W2418024214
article OA: closed CC0 ⤵ 25 in-corpus citations
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This study found that increased MMP-2 activity, associated with decreased TIMP-2, drives early endometriosis development in mice, and curcumin delays this progression by upregulating TIMP-2 and downregulating MT1MMP.

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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.

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Condition tags

endometriosis

MeSH descriptors

Curcumin Endometriosis Endometriosis Matrix Metalloproteinase 2 Peritoneal Diseases Peritoneal Diseases Animals Anti-Inflammatory Agents, Non-Steroidal Curcumin Dose-Response Relationship, Drug Endometriosis Enzyme Activation Enzyme Activation Female Matrix Metalloproteinase 2 Matrix Metalloproteinase Inhibitors Matrix Metalloproteinase Inhibitors Mice Mice, Inbred BALB C Peritoneal Diseases

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