PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis

Wang, Mengxue; Fan, Ruiqi; Jiang, Junyi; Sun, Fangyuan; Sun, Yujun; Wang, Qian; Jiang, Aifang; Yu, Zhenhai; Yang, Tingting

doi:10.1007/s43032-023-01208-w

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…Several studies, including comparative proteomics analyses, have revealed similarities between endometriosis and cancer with respect to metabolic reprogramming. [19][20][21] The expression levels of glycolysis-associated molecules (e.g., hypoxia inducible factor 1 subunit alpha [HIF1A], 22 hexokinase 2 [HK2], 23,24 pyruvate kinase M2 [PKM2], 24 pyruvate dehydrogenase kinase 1 [PDK1], 22,25 glucose-6-phosphate dehydrogenase [G6PD], 26 and lactate dehydrogenase A [LDHA] 22,27 ) were higher in endometriotic lesions than in normal and eutopic endometria (Figure 1①). Indeed, increased glucose consumption and lactate production were observed in pelvic peritoneal endometriosis 25 and stromal cells of endometriotic tissue.…”

Section: Energy Metabolism In Endometriosismentioning

confidence: 99%

The role of mitochondrial dynamics in the pathophysiology of endometriosis

Kobayashi,

Matsubara,

Yoshimoto

et al. 2023

J of Obstet and Gynaecol

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AimEndometriosis is a chronic disease of reproductive age, associated with pelvic pain and infertility. Endometriotic cells adapt to changing environments such as oxidative stress and hypoxia in order to survive. However, the underlying mechanisms remain to be fully elucidated. In this review, we summarize our current understanding of the pathogenesis of endometriosis, focusing primarily on the molecular basis of energy metabolism, redox homeostasis, and mitochondrial function, and discuss perspectives on future research directions.MethodsPapers published up to March 31, 2023 in the PubMed and Google Scholar databases were included in this narrative literature review.ResultsMitochondria serve as a central hub sensing a multitude of physiological processes, including energy production and cellular redox homeostasis. Under hypoxia, endometriotic cells favor glycolysis and actively produce pyruvate, nicotinamide adenine dinucleotide phosphate (NADPH), and other metabolites for cell proliferation. Mitochondrial fission and fusion dynamics may regulate the phenotypic plasticity of cellular energy metabolism, that is, aerobic glycolysis or OXPHOS. Endometriotic cells have been reported to have reduced mitochondrial numbers, increased lamellar cristae, improved energy efficiency, and enhanced cell proliferation and survival. Increased mitochondrial fission and fusion turnover by hypoxic and normoxic conditions suggests an activation of mitochondrial quality control mechanisms. Recently, candidate molecules that influence mitochondrial dynamics have begun to be identified.ConclusionThis review suggests that unique energy metabolism and redox homeostasis driven by mitochondrial dynamics may be linked to the pathophysiology of endometriosis. However, further studies are needed to elucidate the regulatory mechanisms of mitochondrial dynamics in endometriosis.

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Section: Energy Metabolism In Endometriosismentioning

confidence: 99%

The role of mitochondrial dynamics in the pathophysiology of endometriosis

Kobayashi,

Matsubara,

Yoshimoto

et al. 2023

J of Obstet and Gynaecol

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NEK2 promotes the development of ovarian endometriosis and impairs decidualization by phosphorylating FOXO1

Wang,

Sun,

Zhang

et al. 2024

Cell. Mol. Life Sci.

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Ovarian endometriosis is a common gynecological disease, and one of its most significant symptoms is infertility. In patients with endometriosis, defects in endometrial decidualization lead to impaired endometrial receptivity and embryo implantation, thus affecting early pregnancy and women’s desire to have children. However, the mechanisms underlying the development of endometriosis and its associated defective decidualization are unclear. We find that NEK2 expression is increased in the ectopic and eutopic endometrium of patients with endometriosis. Meanwhile, NEK2 interacts with FOXO1 and phosphorylates FOXO1 at Ser184, inhibiting the stability of the FOXO1 protein. Importantly, NEK2-mediated phosphorylation of FOXO1 at Ser184 promotes cell proliferation, migration, invasion and impairs decidualization. Furthermore, INH1, an inhibitor of NEK2, inhibits the growth of ectopic lesions in mouse models of endometriosis and promotes endometrial decidualization in mouse models of artificially induced decidualization. Taken together, these findings indicate that NEK2 regulates the development of endometriosis and associated disorders of decidualization through the phosphorylation of FOXO1, providing a new therapeutic target for its treatment.

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AURKA Enhances the Glycolysis and Development of Ovarian Endometriosis Through ERβ

Sun,

Zhang,

Zhang

et al. 2024

Endocrinology

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Ovarian endometriosis is a benign, estrogen-dependent gynecological disorder. Estrogen receptor beta (ERβ), a nuclear receptor for estradiol, plays an important role in the development of ovarian endometriosis. Here, we investigated the biological significance of Aurora kinase A (AURKA) in ovarian endometriosis and the mechanism by which it regulated ERβ. We used immunohistochemical assays to verify that AURKA and ERβ were highly expressed in ectopic endometrial tissues. Cell proliferation and colony formation assays were used to demonstrate that AURKA promoted the proliferation of endometriosis cells. Wound healing assay, Transwell migration assay and Matrigel invasion assay further show that AURKA enhanced ability of endometriosis cells to migrate and invade. In addition, AURKA was shown to stimulate glycolysis in endometriosis cells by measuring the concentration of glucose and lactate in the cell supernatants. Moreover, the AURKA inhibitor Alisertib was found to inhibit the progression of ovarian endometriosis and glycolysis in a mouse model of endometriosis by measuring ectopic tissues as well as by testing the peritoneal fluid of mice. Furthermore, Co-immunoprecipitation assay showed that AURKA interacted with ERβ. The rescue experiments confirmed that AURKA regulated the development and glycolysis of ovarian endometriosis in an ERβ-dependent manner. In conclusion, AURKA contributed to the development of ovarian endometriosis by upregulating of ERβ. AURKA may represent a new target for the treatment of ovarian endometriosis.

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PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis

Cited by 3 publications

References 45 publications

The role of mitochondrial dynamics in the pathophysiology of endometriosis

The role of mitochondrial dynamics in the pathophysiology of endometriosis

NEK2 promotes the development of ovarian endometriosis and impairs decidualization by phosphorylating FOXO1

AURKA Enhances the Glycolysis and Development of Ovarian Endometriosis Through ERβ

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