Endometriosis is a common gynecological inflammatory disorder characterized by immune system dysregulation, which is involved in lesion initiation and progression. Studies have demonstrated that several cytokines are associated with the evolution of endometriosis, including tumor necrosis factor-a (TNFa). TNFa is a non-glycosylated cytokine protein with potent inflammatory, cytotoxic, and angiogenic potential. In the current study, we examined the ability of TNFa to induce dysregulation of microRNAs (miRNAs) linked to NFkB signaling pathways, thus contributing to the pathogenesis of endometriosis. Using RT-qPCR, the expression of several miRNAs was quantified in primary cells derived from eutopic endometrium of endometriosis subjects (EESC) and normal endometrial stromal cells (NESC), and also TNFa-treated NESCs. The phosphorylation of the pro-inflammatory molecule NF-?B and the candidates of the survival pathways PI3K, AKT, and ERK was measured by western blot analysis. The elevated secretion of TNFa in EESCs downregulates the expression level of several miRNAs significantly in EESCs compared to NESCs. Also, treatment of NESCs with exogenous TNFa significantly reduced the expression of miRNAs in a dose-dependent manner to levels similar to EESCs. In addition, TNFa significantly increased the phosphorylation of the PI3K, AKT, ERK, and NF-?B signaling pathways. Notably, treatment with curcumin (CUR, diferuloylmethane), an anti-inflammatory polyphenol, significantly increased the expression of dysregulated miRNAs in EESC in a dose-dependent manner. Our findings demonstrate that TNFa is upregulated in EESCs, which subsequently dysregulates the expression of miRNAs, contributing to the pathophysiology of endometriotic cells. CUR effectively inhibits the expression of TNFa, subsequently altering miRNA levels and suppressing the phosphorylation of AKT, ERK, and NF-?B.
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Madigan Army Med Ctr, Div Reprod Endocrinol & Infertil, Tacoma, WA 98431 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Burney, R. O.
Hamilton, A. E.
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Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Hamilton, A. E.
Aghajanova, L.
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Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Aghajanova, L.
Vo, K. C.
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Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Vo, K. C.
Nezhat, C. N.
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Stanford Univ, Sch Med, Dept Gynecol & Obstet, Stanford, CA 94305 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Nezhat, C. N.
Lessey, B. A.
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Ctr Womens Med, Reprod Endocrinol & Infertil Div, Greenville, SC USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Lessey, B. A.
Giudice, L. C.
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Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
机构:
Madigan Army Med Ctr, Div Reprod Endocrinol & Infertil, Tacoma, WA 98431 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Burney, R. O.
Hamilton, A. E.
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h-index: 0
机构:
Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Hamilton, A. E.
Aghajanova, L.
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h-index: 0
机构:
Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Aghajanova, L.
Vo, K. C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Vo, K. C.
Nezhat, C. N.
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h-index: 0
机构:
Stanford Univ, Sch Med, Dept Gynecol & Obstet, Stanford, CA 94305 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Nezhat, C. N.
Lessey, B. A.
论文数: 0引用数: 0
h-index: 0
机构:
Ctr Womens Med, Reprod Endocrinol & Infertil Div, Greenville, SC USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
Lessey, B. A.
Giudice, L. C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA