The Autonomic Innervation and Uterine Telocyte Interplay in Leiomyoma Formation

Aleksandrovych, Veronika; Kurnik‐Łucka, Magdalena; Bereza, Tomasz; Białas, Magdalena; Pasternak, Artur; Crețoiu, Dragoș; Walocha, Jerzy; Gil, Krzysztof

doi:10.1177/0963689719833303

Cited by 22 publications

(21 citation statements)

References 57 publications

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“…A recent study shows, for the first time, that there is an interplay between telocytes and autonomic innervation in leiomyomata [92]. TCs decreased in numbers in the leiomyomatous myometrium, suggesting a role for these cells in the control of the microenvironment [92].…”

Section: Telocytes In Uterine and Tubal Diseasesmentioning

confidence: 98%

Telocytes: New Connecting Devices in the Stromal Space of Organs

Crețoiu¹,

Vannucchi²,

Bei³

et al. 2020

Innovations in Cell Research and Therapy

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Telocytes (TCs) represent a new type of interstitial cells, and were discovered by Prof. Popescu and his collaborators from Bucharest in 2005, and described as Interstitial Cajal-Like Cells (ICLCs). In 2010, Prof. Popescu and Prof. Faussone-Pellegrini from Florence, based on their expertise in morphology, agreed that in fact ICLCs were a brand-new entity and they renamed them telocytes. TCs are characterized by specific veil-or ribbon-like extensions called telopodes. Telopodes aid TCs in forming homo-or hetero-cellular contacts; thus, assembling three-dimensional networks that organizes the stromal and the parenchymal components of the organs. TCs can transfer information to neighbor cells ensuring a short-distance communication, and remotely by the release a wide variety of extracellular vesicles: exosomes, ectosomes, and multivesicular bodies. Here, we reviewed the evolution of the interest regarding TCs in different organs, in normal and pathological conditions. The main focus was on the role of TCs in gastrointestinal tract, urinary bladder, reproductive tract, and heart. This chapter sums up information about the possibilities that TCs are capable to behave as sensors/mediators in nervous activity, to represent mesenchymal stem cell precursors in adulthood, and to control and determine the differentiation/maturation of other cell types either during development or in postnatal life.

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Section: Telocytes In Uterine and Tubal Diseasesmentioning

confidence: 98%

Telocytes: New Connecting Devices in the Stromal Space of Organs

Crețoiu¹,

Vannucchi²,

Bei³

et al. 2020

Innovations in Cell Research and Therapy

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“…TCs also form neurological connections. Previous studies have shown the relationship between TCs and uterine autonomic nerves 17 .…”

Section: Introductionmentioning

confidence: 95%

Telocytes Enhances M1 Differentiation and Phagocytosis While Inhibits Mitochondria-Mediated Apoptosis Via Activation of NF-κB in Macrophages

et al. 2021

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Telocytes (TCs), which are a recently discovered interstitial cell type present in various organs and tissues, perform multiple biological functions and participate in extensive crosstalk with neighboring cells. Endometriosis (EMs) is a gynecological disease characterized by the presence of viable endometrial debris and impaired macrophage phagocytosis in the peritoneal environment. Here, CD34/vimentin-positive TCs were co-cultured with RAW264.7 cells in vitro. M1/M2 differentiation-related markers were detected; phagocytosis, energy metabolism, proliferation, apoptosis, and pathway mechanisms were studied; and the mitochondrial membrane potential (ΔΨm) was measured. Furthermore, in an EMs mouse model, the differentiation of macrophages in response to treatment with TC-conditioned medium (TCM) in vivo was studied. The results showed that upon in vitro co-culture with TCM, RAW264.7 cells differentiated more toward the M1 phenotype with enhancement of phagocytosis, increase in energy metabolism and proliferation owing to reduced the loss of ΔΨm, and suppression of dexamethasone-induced apoptosis. Further, along with the activation of NF-κB, Bcl-2 and Bcl-xl, the expression of Bax, cleaved-caspase9, and cleaved-caspase3 reduced in RAW264.7 cells. In addition, the M1 subtype was found to be the dominant phenotype among tissue and peritoneal macrophages in the EMs model subjected to in vivo TCM treatment. In conclusion, TCs enhanced M1 differentiation and phagocytosis while inhibiting apoptosis via the activation of NF-κB in macrophages, which potentially inhibited the onset of EMs. Our findings provide a potential research target and the scope for developing a promising therapeutic strategy for EMs.

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“…The aforementioned epigenetic associations of CACNA1A support the gene's involvement in epigenetics of tumorogenesis. Interestingly, a previous study demonstrated that innervation of the uterus is involved in multiple pathophysiological processes and suggests that autonomic innervations together with interstitial telocytes are involved in the microenvironmental imbalance of UL [48]. Moreover, the difference in adrenergic and cholinergic innervation between normal myometrium and fibroid tumors demonstrates the pivotal role of the neuronal component in the formation of UL [48].…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Synaptic Signaling Genes Is Involved in Biology of Uterine Leiomyoma

Krsteski

Gorenjak

But

et al. 2021

Genes

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Uterine leiomyomas are tumors, which are hormone driven and originate from the smooth muscle layer of the uterine wall. In addition to known genes in leiomyoma pathogenesis, recent approaches also highlight epigenetic malfunctions as an important mechanism of gene dysregulation. RNA sequencing raw data from pair-matched normal myometrium and fibroid tumors from two independent studies were used as discovery and validation sets and reanalyzed. RNA extracted from normal myometrium and fibroid tumors from 58 Slovenian patients was used as independent confirmation of most significant differentially expressed genes. Subsequently, GWA data from leiomyoma patients were used in order to identify genetic variants at epigenetic marks. Gene Ontology analysis of the overlap of two independent RNA-seq analyses showed that NPTX1, NPTX2, CHRM2, DRD2 and CACNA1A were listed as significant for several enriched GO terms. All five genes were subsequently confirmed in the independent Slovenian cohort. Additional integration and functional analysis showed that genetic variants in these five gene regions are listed at a chromatin structure and state, predicting promoters, enhancers, DNase hypersensitivity and altered transcription factor binding sites. We identified a unique subgroup of dysregulated synaptic signaling genes involved in the biology and pathogenesis of leiomyomas, adding to the complexity of tumor biology.

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The Autonomic Innervation and Uterine Telocyte Interplay in Leiomyoma Formation

Cited by 22 publications

References 57 publications

Telocytes: New Connecting Devices in the Stromal Space of Organs

Telocytes: New Connecting Devices in the Stromal Space of Organs

Telocytes Enhances M1 Differentiation and Phagocytosis While Inhibits Mitochondria-Mediated Apoptosis Via Activation of NF-κB in Macrophages

Dysregulation of Synaptic Signaling Genes Is Involved in Biology of Uterine Leiomyoma

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