Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target

Zheng, Hanxi; Liu, Xishi; Guo, Sun‐Wei

doi:10.1002/rmb2.12531

Cited by 3 publications

(1 citation statement)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Trichostatin A, an HDAC inhibitor, suppressed endometriotic lesion growth and hyperalgesia in a mouse model of endometriosis (Lu, Nie et al, 2010). A recent study revealed that HDAC8 is progressively and aberrantly overexpressed as endometriotic lesions advance (Zheng et al, 2023a, Zheng, Liu et al, 2023b). However, this study did not elucidate the role of HDAC8 in the progression of endometriosis.…”

Section: Discussionmentioning

confidence: 99%

N-Myc and STAT Interactor is an endometriosis suppressor

Park,

Guan,

Han

2024

Preprint

View full text Add to dashboard Cite

In patients with endometriosis, refluxed endometrial fragments evade host immunosurveillance, developing into endometriotic lesions. However, the mechanisms underlying this evasion have not been fully elucidated. N-Myc and STAT Interactor (NMI) have been identified as key players in host immunosurveillance, including interferon (IFN)-induced cell death signaling pathways. NMI levels are markedly reduced in the stromal cells of human endometriotic lesions due to modulation by the Estrogen Receptor beta/Histone Deacetylase 8 axis. Knocking down NMI in immortalized human endometrial stromal cells (IHESCs) led to elevated RNA levels of genes involved in cell-to-cell adhesion and extracellular matrix signaling following IFNA treatment. Furthermore, NMI knockdown inhibited IFN-regulated canonical signaling pathways, such as apoptosis mediated by Interferon Stimulated Gene Factor 3, and necroptosis upon IFNA treatment. In contrast, NMI knockdown with IFNA treatment activated non-canonical IFN-regulated signaling pathways that promote proliferation, including β-Catenin and AKT signaling. Moreover, NMI knockdown in IHESCs stimulated ectopic lesions' growth in mouse endometriosis models. Therefore, NMI is a novel endometriosis suppressor, enhancing apoptosis and inhibiting proliferation and cell adhesion of endometrial cells upon IFN exposure.

show abstract

Section: Discussionmentioning

confidence: 99%

N-Myc and STAT Interactor is an endometriosis suppressor

Park,

Guan,

Han

2024

Preprint

View full text Add to dashboard Cite

show abstract

The role of fibrosis in endometriosis: a systematic review

Vissers,

Giacomozzi,

Verdurmen

et al. 2024

Human Reproduction Update

View full text Add to dashboard Cite

BACKGROUND Fibrosis is an important pathological feature of endometriotic lesions of all subtypes. Fibrosis is present in and around endometriotic lesions, and a central role in its development is played by myofibroblasts, which are cells derived mainly after epithelial-to-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT). Transforming growth factor-β (TGF-β) has a key role in this myofibroblastic differentiation. Myofibroblasts deposit extracellular matrix (ECM) and have contracting abilities, leading to a stiff micro-environment. These aspects are hypothesized to be involved in the origin of endometriosis-associated pain. Additionally, similarities between endometriosis-related fibrosis and other fibrotic diseases, such as systemic sclerosis or lung fibrosis, indicate that targeting fibrosis could be a potential therapeutic strategy for non-hormonal therapy for endometriosis. OBJECTIVE AND RATIONALE This review aims to summarize the current knowledge and to highlight the knowledge gaps about the role of fibrosis in endometriosis. A comprehensive literature overview about the role of fibrosis in endometriosis can improve the efficiency of fibrosis-oriented research in endometriosis. SEARCH METHODS A systematic literature search was performed in three biomedical databases using search terms for ‘endometriosis’, ‘fibrosis’, ‘myofibroblasts’, ‘collagen’, and ‘α-smooth muscle actin’. Original studies were included if they reported about fibrosis and endometriosis. Both preclinical in vitro and animal studies, as well as research concerning human subjects were included. OUTCOMES Our search yielded 3441 results, of which 142 studies were included in this review. Most studies scored a high to moderate risk of bias according to the bias assessment tools. The studies were divided in three categories: human observational studies, experimental studies with human-derived material, and animal studies. The observational studies showed details about the histologic appearance of fibrosis in endometriosis and the co-occurrence of nerves and immune cells in lesions. The in vitro studies identified several pro-fibrotic pathways in relation to endometriosis. The animal studies mainly assessed the effect of potential therapeutic strategies to halt or regress fibrosis, for example targeting platelets or mast cells. WIDER IMPLICATIONS This review shows the central role of fibrosis and its main cellular driver, the myofibroblast, in endometriosis. Platelets and TGF-β have a pivotal role in pro-fibrotic signaling. The presence of nerves and neuropeptides is closely associated with fibrosis in endometriotic lesions, and is likely a cause of endometriosis-associated pain. The process of fibrotic development after EMT and FMT shares characteristics with other fibrotic diseases, so exploring similarities in endometriosis with known processes in diseases like systemic sclerosis, idiopathic pulmonary fibrosis or liver cirrhosis is relevant and a promising direction to explore new treatment strategies. The close relationship with nerves appears rather unique for endometriosis-related fibrosis and is not observed in other fibrotic diseases. REGISTRATION NUMBER N/A.

show abstract

N-Myc and STAT Interactor is an Endometriosis Suppressor

Park,

Guan,

Han

2024

IJMS

View full text Add to dashboard Cite

In patients with endometriosis, refluxed endometrial fragments evade host immunosurveillance, developing into endometriotic lesions. However, the mechanisms underlying this evasion have not been fully elucidated. N-Myc and STAT Interactor (NMI) have been identified as key players in host immunosurveillance, including interferon (IFN)-induced cell death signaling pathways. NMI levels are markedly reduced in the stromal cells of human endometriotic lesions due to modulation by the Estrogen Receptor beta/Histone Deacetylase 8 axis. Knocking down NMI in immortalized human endometrial stromal cells (IHESCs) led to elevated RNA levels of genes involved in cell-to-cell adhesion and extracellular matrix signaling following IFNA treatment. Furthermore, NMI knockdown inhibited IFN-regulated canonical signaling pathways, such as apoptosis mediated by Interferon Stimulated Gene Factor 3 and necroptosis upon IFNA treatment. In contrast, NMI knockdown with IFNA treatment activated non-canonical IFN-regulated signaling pathways that promote proliferation, including β-Catenin and AKT signaling. Moreover, NMI knockdown in IHESCs stimulated ectopic lesions’ growth in mouse endometriosis models. Therefore, NMI is a novel endometriosis suppressor, enhancing apoptosis and inhibiting proliferation and cell adhesion of endometrial cells upon IFN exposure.

show abstract

Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target

Cited by 3 publications

References 103 publications

N-Myc and STAT Interactor is an endometriosis suppressor

N-Myc and STAT Interactor is an endometriosis suppressor

The role of fibrosis in endometriosis: a systematic review

N-Myc and STAT Interactor is an Endometriosis Suppressor

Contact Info

Product

Resources

About