TNFα-Induced Altered miRNA Expression Links to NF-κB Signaling Pathway in Endometriosis

被引:8
作者
Banerjee, Saswati [1 ]
Xu, Wei [1 ]
Doctor, Aaron [2 ]
Driss, Adel [1 ]
Nezhat, Ceana [3 ]
Sidell, Neil [4 ]
Taylor, Robert N. [5 ]
Thompson, Winston E. [1 ,2 ]
Chowdhury, Indrajit [2 ]
机构
[1] Morehouse Sch Med, Dept Physiol, Atlanta, GA 30310 USA
[2] Morehouse Sch Med, Dept Obstet & Gynecol, 720 Westview Dr Southwest, Atlanta, GA 30310 USA
[3] Nezhat Med Ctr, 5555 Peachtree Dunwoody Rd, Atlanta, GA 30342 USA
[4] Emory Univ, Dept Gynecol & Obstet, Sch Med, Atlanta, GA 30322 USA
[5] Univ Buffalo, Jacobs Sch Med & Biomed Sci, Dept Obstet & Gynecol, Buffalo, NY 14203 USA
基金
美国国家卫生研究院;
关键词
endometriosis; TNF & alpha; miRNA; signaling; FACTOR-KAPPA-B; TNF-ALPHA; MICRORNA REGULATION; PERITONEAL-FLUID; STROMAL CELLS; WOMEN; PATHOGENESIS; PROLIFERATION; INFLAMMATION; GENES;
D O I
10.1007/s10753-023-01862-x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:2055 / 2070
页数:16
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