Molecular mechanism of autophagy and apoptosis in endometriosis: Current understanding and future research directions

Kobayashi, Hiroshi; Imanaka, Shogo; Yoshimoto, Chiharu; Matsubara, Sho; Shigetomi, Hiroshi

doi:10.1002/rmb2.12577

Cited by 3 publications

(2 citation statements)

References 120 publications

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“…Beclin1 promotes autophagy and LC3 protein levels reflects autophagy induction ( 15 ). For more details, see our recent review article on the molecular mechanisms of autophagy and apoptosis in endometriosis ( 16 ). Autophagy can determine the cellular fate ( 14 ).…”

Section: Molecular and Regulatory Network Mechanisms Controlling Auto...mentioning

confidence: 99%

“…The development and progression of endometriosis may rely not only on the inherent proliferative nature but also on the ever-changing surrounding microenvironment ( 31 , 32 ). Endometriotic lesion growth can be promoted via multiple intrinsic pathways, including not only estrogen and PI3K/AKT/mTOR as aforementioned, but also mitogen-activated protein kinases (MAPK)/mitogen-activated protein kinase kinase/extracellular-signal-regulated kinases and nuclear factor-kappa B ( 33 , 34 ), while it may also be influenced by extrinsic factors such as iron overload and hypoxia ( 16 , 35 , 36 ). The present section mainly focused on the molecular mechanisms of iron, hypoxia-inducible factor 1 (HIF-1) and PI3K/AKT/mTOR pathways that regulate cell survival and summarized their roles in the development and progression of endometriosis.…”

Section: Molecular and Regulatory Network Mechanisms Controlling Iron...mentioning

confidence: 99%

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Role of autophagy and ferroptosis in the development of endometriotic cysts (Review)

Kobayashi,

Imanaka,

Yoshimoto

et al. 2024

Int J Mol Med

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It is considered that the etiology of endometriosis is retrograde menstruation of endometrial tissue. Although shed endometrial cells are constantly exposed to a challenging environment with iron overload, oxidative stress and hypoxia, a few cells are able to survive and continue to proliferate and invade. Ferroptosis, an iron-dependent form of non-apoptotic cell death, is known to play a major role in the development and course of endometriosis. However, few papers have concentrated on the dynamic interaction between autophagy and ferroptosis throughout the progression of diseases. The present review summarized the current understanding of the mechanisms underlying autophagy and ferroptosis in endometriosis and discuss their role in disease development and progression. For the present narrative review electronic databases including PubMed and Google Scholar were searched for literature published up to the October 31, 2023. Autophagy and ferroptosis may be activated at early stages in endometriosis development. On the other hand, excessive activation of intrinsic pathways (e.g., estrogen and mechanistic target of rapamycin) may promote disease progression through autophagy inhibition. Furthermore, suppression of ferroptosis may cause further progression of endometriotic lesions. In conclusion, the autophagy and ferroptosis pathways may play a dual role in disease initiation and progression. The present review discussed the temporal transition of non-apoptotic cell death regulation during disease progression from retrograde endometrium to early lesions to established lesions.

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Section: Molecular and Regulatory Network Mechanisms Controlling Auto...mentioning

confidence: 99%

Section: Molecular and Regulatory Network Mechanisms Controlling Iron...mentioning

confidence: 99%

Role of autophagy and ferroptosis in the development of endometriotic cysts (Review)

Kobayashi,

Imanaka,

Yoshimoto

et al. 2024

Int J Mol Med

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mTOR inhibitors as potential therapeutics for endometriosis: a narrative review

Nakamura,

Tanaka,

Amano

et al. 2024

Molecular Human Reproduction

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Mammalian target of rapamycin (mTOR) inhibitors have been used clinically as anticancer and immunosuppressive agents for over 20 years, demonstrating their safety after long-term administration. These inhibitors exhibit various effects, including inhibition of cell proliferation, interaction with the oestrogen and progesterone pathways, immunosuppression, regulation of angiogenesis, and control of autophagy. We evaluated the potential of mTOR inhibitors as therapeutic agents for endometriosis, examined the secondary benefits related to reproductive function, and assessed how their side effects can be managed. We conducted a thorough review of publications on the role of the mTOR pathway and the effectiveness of mTOR inhibitors in endometriosis patients. These results indicate that the mTOR pathway is activated in endometriosis. Additionally, mTOR inhibitors have shown efficacy as monotherapies for endometriosis. They may alleviate resistance to hormonal therapy in endometriosis, suggesting a potential synergistic effect when used in combination with hormonal therapy. The potential reproductive benefits of mTOR inhibitors include decreased miscarriage rates, improved implantation, and prevention of age-related follicular loss and ovarian hyperstimulation syndrome. Activation of the mTOR pathway has also been implicated in the malignant transformation of endometriosis. Preclinical studies suggest that the dosage of mTOR inhibitors needed for treating endometriosis may be lower than that required for anticancer or immunosuppressive therapy, potentially reducing dosage-dependent side effects. In conclusion, while mTOR inhibitors, which allow for pregnancy during oral administration, show potential for clinical use in all stages of endometriosis, current evidence is limited to preclinical studies, and further research is needed to confirm clinical effectiveness.

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Rethinking the pathogenesis of endometriosis: Complex interactions of genomic, epigenetic, and environmental factors

Kobayashi,

Imanaka,

Yoshimoto

et al. 2024

J of Obstet and Gynaecol

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AimEndometriosis is a complex, multifactorial disease. Recent advances in molecular biology underscore that somatic mutations within the epithelial component of the normal endometrium, alongside aberrant epigenetic alterations within endometrial stromal cells, may serve as stimulators for the proliferation of endometriotic tissue within the peritoneal cavity. Nevertheless, pivotal inquiries persist: the deterministic factors driving endometriosis development in certain women while sparing others, notwithstanding comparable experiences of retrograde menstruation. Within this review, we endeavor to synopsize the current understanding of diverse pathophysiologic mechanisms underlying the initiation and progression of endometriosis and delineate avenues for future research.MethodsA literature search without time restriction was conducted utilizing PubMed and Google Scholar.ResultsGiven that aberrant clonal expansion stemming from cancer‐associated mutations is common in normal endometrial tissue, only endometrial cells harboring mutations imparting proliferative advantages may be selected for survival outside the uterus. Endometriotic cells capable of engendering metabolic plasticity and modulating mitochondrial dynamics, thereby orchestrating responses to hypoxia, oxidative stress, inflammation, hormonal stimuli, and immune surveillance, and adeptly acclimating to their harsh surroundings, stand a chance at viability.ConclusionThe genesis of endometriosis appears to reflect the evolutionary principles of mutation, selection, clonal expansion, and adaptation to the environment.

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Molecular mechanism of autophagy and apoptosis in endometriosis: Current understanding and future research directions

Cited by 3 publications

References 120 publications

Role of autophagy and ferroptosis in the development of endometriotic cysts (Review)

Role of autophagy and ferroptosis in the development of endometriotic cysts (Review)

mTOR inhibitors as potential therapeutics for endometriosis: a narrative review

Rethinking the pathogenesis of endometriosis: Complex interactions of genomic, epigenetic, and environmental factors

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