The Expression and Cellular Localisation of Neurotrophin and Neural Guidance Molecules in Peritoneal Ectopic Lesions

Asally, Razan; Markham, Robert; Manconi, Frank

doi:10.1007/s12035-018-1348-6

Cited by 15 publications

(10 citation statements)

References 25 publications

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“…Endometriosis approximately afflicts 10-15% of women of childbearing age, and only symptomatic treatment options are available owing to the poorly understood pathogenesis of this condition, underscoring requirements for generating novel treatment strategies for this condition (Falcone and Flyckt, 2018;Asally et al, 2019). Autophagy is a key regulator of the onset and progression of endometriosis (Shen et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Hyaluronic Acid-Modified Nanoplatforms as a Vector for Targeted Delivery of Autophagy-Related Gene to the Endometriotic Lesions in Mice

Zhao

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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This investigation probed endometriosis treatment using targeted nanoparticles (NPs) to modulate autophagic activity. To that end, a novel form of polymer-based NP gene delivery platform consisting of polyethyleneimine (PEI) conjugated to stearic acid (SA) and nucleotides (DNA/siRNAs) and enclosed by hyaluronic acid (HA) was prepared. CD44 is highly upregulated in cystic lesions, and HA–CD44 binding in this specific nanoplatform was used to achieve targeted drug delivery to CD44-expression endometriotic tissues. The expression of autophagy-related genes was modulated to explore the importance of this process in the development of endometriosis. By inducing autophagic activity, we were able to reduce the size of endometriotic cysts and suppress the development of ectopic endometrium. To further confirm the relationship between autophagic activity and this disease in humans and animals, numbers of autophagic vesicles and autophagic protein expression were assessed in lesion tissue samples from patients, revealing there may be consistency between animal and human data. Overall, these data revealed the ability of this (PEI–SA/DNA) HA gene delivery system to regulate autophagic activity and, thereby, aid in the treatment of endometriosis.

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Section: Discussionmentioning

confidence: 99%

Hyaluronic Acid-Modified Nanoplatforms as a Vector for Targeted Delivery of Autophagy-Related Gene to the Endometriotic Lesions in Mice

Zhao

Zhang

et al. 2022

Front. Bioeng. Biotechnol.

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“…Ectopic endometrial stromal cells can secrete neurotrophic factors, such as NGF, NT-3, TrkB, TXA2, and GDNF (Barcena de Arellano et al 2011, 2013a, Greaves et al 2015, Yan et al 2017a, and axon guidance molecules such as Semaphorin 3E and SLIT/ ROBO (Greaves et al 2014, Asally et al 2019, resulting in increased nerve fiber density and hyperinnervation in lesions (Wang et al 2009a,b, Zhang et al 2010. Moreover, eutopic endometrium from women with endometriosis, and possibly with adenomyosis as well, can promote neuroangiogenesis through exosome release (Sun et al 2019).…”

Section: Cracking the Enigma Of Adenomyosis R107mentioning

confidence: 99%

Cracking the enigma of adenomyosis: an update on its pathogenesis and pathophysiology

Guo

2022

Reproduction

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Traditionally considered as an enigmatic disease, adenomyosis is a uterine disease that affects many women of reproductive age, and is a contributing factor for pelvic pain, heavy menstrual bleeding (HMB), and subfertility. In this review, the new development on the pathogenesis and pathophysiology of adenomyosis has been summarized, along with their clinical implications. After reviewing the progress on our understanding of the pathogenesis and describing the prevailing theories, in conjunction with their deficiencies, a new hypothesis, called endometrial-myometrial interface disruption (EMID), which is backed by extensive epidemiologic data and demonstrated by a mouse model, is reviewed, along with recent data implicating the role of Schwann cells in the EMI area in the genesis of adenomyosis. Additionally, the natural history of adenomyotic lesions is elaborated and underscores that, ] in essence, adenomyotic lesions are fundamentally wounds undergoing repeated tissue injury and repair (ReTIAR), which progress to fibrosis through epithelial-mesenchymal transition, fibroblast-to-myofibroblast transdifferentiation, and smooth muscle metaplasia. Increasing lesional fibrosis propagates into the neighboring the EMI and endometrium. The increased endometrial fibrosis, with ensuing greater tissue stiffness, results in attenuated prostaglandin E2 (PGE2) and hypoxia signaling, impairing endometrial repair and causing HMB. Compared with adenomyosis-associated HMB, the mechanisms underlying adenomyosis-associated pain is less understood, but presumably involves increased uterine contractility, hyperinnervation, increased lesional production of pain mediators, and central sensitization. Viewed through the prism of ReTIAR, new imaging technique can be used to diagnosis adenomyosis and possibly help to choose the best treatment modality.

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“…As opposed to NGF and BDNF which have been extensively studied in endometriosis and found to be dysregulated and overexpressed, relatively few observations about NT-3 and NT-4/5 have been published to date. Both factors have been found to be expressed in the lesions, 38 but there is currently no data suggesting that they play a critical role in endometriosis pathophysiology.…”

Section: Bdnf/trkbmentioning

confidence: 99%

The role of peripheral nerve signaling in endometriosis

et al. 2021

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A hallmark of endometriosisa chronic debilitating condition whose causes are poorly understoodis neuronal innervation of lesions. Recent evidence demonstrates that the peripheral nervous system plays an important role in the pathophysiology of this disease. Sensory nerves, which surround and innervate endometriotic lesions, not only drive the chronic and debilitating pain associated with endometriosis but also contribute to a pro-growth phenotype by secreting neurotrophic factors and interacting with surrounding immune cells. The diverse array of contributions that neurons play in endometriosis indicate that it should be considered as a nerve-centric disease. This review is focused on the emerging field of exoneural biology and how it applies to the field of endometriosis, in particular the role that peripheral nerves play in driving and maintaining endometriotic lesions. A better understanding of the mechanisms of neuronal contribution to endometriosis, as well as their interactions with accompanying stromal and immune cells, will unearth novel disease-relevant pathways and targets, providing additional, more selective therapeutic horizons.

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The Expression and Cellular Localisation of Neurotrophin and Neural Guidance Molecules in Peritoneal Ectopic Lesions

Cited by 15 publications

References 25 publications

Hyaluronic Acid-Modified Nanoplatforms as a Vector for Targeted Delivery of Autophagy-Related Gene to the Endometriotic Lesions in Mice

Hyaluronic Acid-Modified Nanoplatforms as a Vector for Targeted Delivery of Autophagy-Related Gene to the Endometriotic Lesions in Mice

Cracking the enigma of adenomyosis: an update on its pathogenesis and pathophysiology

The role of peripheral nerve signaling in endometriosis

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