Decreased Indian hedgehog signaling activates autophagy in endometriosis and adenomyosis
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Decreased Indian hedgehog signaling in endometriosis and adenomyosis activates autophagy, potentially promoting aberrant endometrial cell survival.
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Abstract
Indian hedgehog (Ihh) signaling regulates endometrial receptivity and is an indispensable mediator of embryonic implantation. Hedgehog signaling is known to regulate autophagy, and aberrant regulation of autophagy is critically implicated in the pathogenesis of endometriosis and adenomyosis. However, potential dysregulation of Ihh signaling and its role in autophagy modulation in these diseases remain obscure. In this study, we found that components of Ihh signaling were significantly decreased, whereas the autophagy marker protein, LC3BII, was significantly increased in endometrial tissues of women with endometriosis or adenomyosis. Inhibition of Ihh signaling with the small-molecule inhibitor GANT61 or Gli1 silencing in primary endometrial stromal cells increased autophagic activity, as measured by LC3 turnover assay and tandem mCherry-eGFP-LC3B fluorescence microscopy. Furthermore, we observed that GANT61 treatment significantly attenuated hydrogen peroxide-induced cell death, whereas disruption of autophagy with chloroquine diminished this effect. Collectively, these findings reveal that Ihh signaling is suppressed in endometrial tissues of patients with endometriosis or adenomyosis. This abnormal decrease may contribute to endometrial autophagy activation, which may promote aberrant survival of endometrial cells in ectopic sites in these two gynecological diseases.
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Cited by (12)
- Dysregulated autophagy in endometriosis: molecular mechanisms, controversies, and clinical implications 2025
- Effects of Shixiao Huoxue Decoction on pain, tumor necrosis factor-α, and interleukin-8 in patients with adenomyosis 2024
- Controversial Roles of Autophagy in Adenomyosis and Its Implications for Fertility Outcomes-A Systematic Review 2024
- Hupo powder promotes autophagy of menstrual blood-derived stem cells from patients with endometriosis 2023
- Towards a Better Understanding of Endometriosis-Related Infertility: A Review on How Endometriosis Affects Endometrial Receptivity 2023
- The Pathological Role of miRNAs in Endometriosis 2023
- Insights on Adenomyosis Development 2022
- Hyaluronic Acid-Modified Nanoplatforms as a Vector for Targeted Delivery of Autophagy-Related Gene to the Endometriotic Lesions in Mice 2022
- How does adenomyosis impact endometrial receptivity? An updated systematic review of clinical and molecular insights 2022
- Molecular Targets for Nonhormonal Treatment Based on a Multistep Process of Adenomyosis Development 2022
- Deficiency of MST1 in endometriosis related peritoneal macrophages promoted the autophagy of ectopic endometrial stromal cells by IL-10 2022
- The expression of <i>BECN1, LC3B</i> , and <i>BCL2</i> genes in eutopic endometrium of patients with adenomyosis: A cross-sectional study 2021
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