Matrix Metalloproteinases and Tace Play A Role in The Pathogenesis of Endometriosis

Constanze Gottschal, C Gottschalk, K Malberg, M Arndt, Marco Arndt, Johannes Schmitt, J Schmitt, Albert Roessner, A Roessner, D Schultze, Dagmar Schultze, J Kleinstein, S Ansorge, Siegfried Ansorge
Advances in experimental medicine and biology · 2006 · vol. 477 , pp. 483–486 · doi:10.1007/0-306-46826-3_49 · PMID:10849774 · W1568126922
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⚙ AI-generated summary by claude@2026-06, 2026-06-06 ⓘ

Endometriotic tissues exhibited higher MMP-1 and TACE protein expression and lower TIMP-1 and -2 expression compared to normal endometrium, suggesting roles in disease pathogenesis.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-06 ⓘ

This study examined the expression of matrix metalloproteinases MMP-1, -2, -3, and -9, their inhibitors TIMP-1 and TIMP-2, the enzyme TACE, and TNF-α in endometriotic tissue versus normal endometrium using immunohistochemistry and in situ hybridization on formalin-fixed paraffin sections, with quantitative PCR for TACE mRNA in fresh tissue. The authors found significantly higher protein expression of MMP-1 and TACE and significantly lower protein expression of TIMP-1 and TIMP-2 in endometriotic tissue compared with endometrium. They propose that increased TACE expression enhances conversion of membrane-bound proTNF-α to soluble TNF-α, which can stimulate increased MMP-1 secretion, and that reduced TIMP levels reflect a proteinase inhibitor imbalance. This paper is centrally about endometriosis — specifically investigating how MMP/TIMP expression and TACE-mediated TNF-α processing relate to endometriosis pathogenesis.

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Abstract

Endometriosis, a benign gynecologic disorder, occurs in about 10% of women in reproductive age and in up to 50% of women with infertility. The basic etiologic factors causing this disease are unknown as yet. Matrix metalloproteinases (MMP) are involved in degradation of the extracellular matrix (ECM). Their proteolytic activity is regulated by tissue inhibitors of metalloproteinases (TIMPs). Tumor necrosis factor-alpha converting enzyme (TACE) is a membrane-bound disintegrin metalloproteinase that processes the membrane-associated cytokine proTNF-alpha to its mature soluble form. TNF-alpha induces the secretion of several MMPs. In order to study the expression of MMP-1, -2, -3 and -9, TIMP-1 and -2, TACE and TNF-alpha in endometrium and endometriotic tissue, we investigated formalin-fixed paraffin sections of endometriotic tissues and normal endometrium with immunohistochemical techniques and in situ hybridisation. Furthermore, quantitative PCR was used for quantification of TACE-mRNA in fresh tissue. We found in this study significant higher protein expression of MMP-1 and TACE and significant lower protein expression of TMP-1 and -2 in endometriotic tissue compared to endometrium. This data may suggest that high TACE expression causes the increased conversion of membrane-bound proTNF-alpha into its soluble form, which stimulates the increased secretion of MMP-1. The simultaneous deficiency of TIMP-1 and -2 in endometriotic tissue suppose an additional proteinase inhibitor imbalance in endometriosis.

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Condition tags

endometriosisinfertility

MeSH descriptors

Endometriosis Metalloendopeptidases ADAM17 Protein ADAM Proteins Endometriosis Endometriosis Endometrium Endometrium Enzyme Induction Female Humans Matrix Metalloproteinase 1 Matrix Metalloproteinase 1 Matrix Metalloproteinase 2 Matrix Metalloproteinase 2 Matrix Metalloproteinase 3 Matrix Metalloproteinase 3 Matrix Metalloproteinase 9 Matrix Metalloproteinase 9 Metalloendopeptidases

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