HucMSCs-exosomes containing miR-21 promoted estrogen production in ovarian granulosa cells via LATS1-mediated phosphorylation of LOXL2 and YAP

Cai, Junhong; Sun, Yuting; Bao, Shan

doi:10.1016/j.ygcen.2022.114015

Cited by 21 publications

(18 citation statements)

References 31 publications

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“…However, the role of miRNA in follicular development and atresia and its relationship with premature ovarian failure are still unclear. Many miRNAs are highly conserved, and their expression is tissue-specific, reflecting that they have important physiological functions and play an important role in the regulation of cell growth and development, including cell proliferation, differentiation, and apoptosis [ 13 , 14 ]. The experiment elucidated the effect and underlying mechanism of human umbilical cord mesenchymal stem cells (HUCMSCs) in premature ovarian failure.…”

Section: Introductionmentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cells Improve Premature Ovarian Failure through Cell Apoptosis of miR-100-5p/NOX4/NLRP3

Niu

Yang

Luo

et al. 2022

BioMed Research International

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Premature ovarian failure refers to a series of symptoms of perimenopausal hot flashes, night sweats, decreased libido, vaginal dryness, insomnia, reduced menstruation, sparse hair, even amenorrhea, and even infertility before the age of 40 due to the decline of ovarian function. Premature ovarian failure is a common and difficult disease in gynecology. Its prevalence is increasing gradually, and the trend is younger. The aim of this experiment was to elucidate the role of human umbilical cord mesenchymal stem cells (HUCMSCs) in premature ovarian failure and its mechanism. HUCMSCs, KGN cells, and HEK293T cells were used in this experiment. Quantitative PCR and microarray analysis, ELISA inflammation and oxidative stress kits, RNA pull-down assay, luciferase reporter assay, proliferation assay, EDU staining, and Western blot analysis were used. In an in vitro model of premature ovarian failure, HUCMSCs attenuated inflammatory response, oxidative stress, and apoptosis. HUCMSCs ameliorated the premature ovarian failure model. The miR-100-5p expression was induced by HUCMSCs through methylation. miR-100-5p regulation influenced the role of HUCMSCs in an in vitro model of premature ovarian failure. HUCMSCs inhibited the in vitro expression of NOX4, NLRP3, and GSDMD proteins in the model. NOX4/NLRP3 signaling pathway affects the role of HUCMSCs in an in vitro model of premature ovarian failure through miR-100-5p. This experiment elucidated the role of HUCMSCs in premature ovarian failure and its mechanism, with a view to providing a clinical reference.

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Section: Introductionmentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cells Improve Premature Ovarian Failure through Cell Apoptosis of miR-100-5p/NOX4/NLRP3

Niu

Yang

Luo

et al. 2022

BioMed Research International

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“…Cai et al. also found that hUMSCs-derived miR-21 could inhibit the expression of LATS1, so as to reduce phosphorylated LOXL2 and YAP, and ultimately promote E2 secretion in ovarian GCs ( 196 ). Moreover, hUMSCs-derived miR-126-3p promote proliferation while inhibit the apoptosis of GCs through PIK3R2/PI3K/AKT/mTOR pathway ( 197 ).…”

Section: Exosomesmentioning

confidence: 99%

“…Li Z et al revealed that hUMSCs-derived exosome significantly ameliorated ovarian function and reproductive ability of POF mice models through promoting GCs proliferation via the Hippo signaling pathway (195). Cai et al also found that hUMSCs-derived miR-21 could inhibit the expression of LATS1, so as to reduce phosphorylated LOXL2 and YAP, and ultimately promote E2 secretion in ovarian GCs (196). Moreover, hUMSCs-derived miR-126-3p promote proliferation while inhibit the apoptosis of GCs through PIK3R2/PI3K/AKT/mTOR pathway (197).…”

Section: Exosomesmentioning

confidence: 99%

Bone marrow mesenchymal stem cells in premature ovarian failure: Mechanisms and prospects

Huang

Zhu²,

Liu³

et al. 2022

Front. Immunol.

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Premature ovarian failure (POF) is a common female reproductive disorder and characterized by menopause, increased gonadotropin levels and estrogen deficiency before the age of 40 years old. The etiologies and pathogenesis of POF are not fully clear. At present, hormone replacement therapy (HRT) is the main treatment options for POF. It helps to ameliorate perimenopausal symptoms and related health risks, but can’t restore ovarian function and fertility fundamentally. With the development of regenerative medicine, bone marrow mesenchymal stem cells (BMSCs) have shown great potential for the recovery of ovarian function and fertility based on the advantages of abundant sources, high capacity for self-renewal and differentiation, low immunogenicity and less ethical considerations. This systematic review aims to summarize the possible therapeutic mechanisms of BMSCs for POF. A detailed search strategy of preclinical studies and clinical trials on BMSCs and POF was performed on PubMed, MEDLINE, Web of Science and Embase database. A total of 21 studies were included in this review. Although the standardization of BMSCs need more explorations, there is no doubt that BMSCs transplantation may represent a prospective therapy for POF. It is hope to provide a theoretical basis for further research and treatment for POF.

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“…miRNA is a distinct class of small (approximately 22 nucleotides), single-stranded, and non-coding RNAs, and play critical functions in the regulation of cellular gene expression by binding to complementary sequences in the target mRNAs, leading to either translational repression or target degradation of the specific mRNAs ( Ha and Kim, 2014 ). Several studies indicate that miRNA carried by EVs plays a key role in the treatment of POI ( Xiao et al, 2016 ; Ding et al, 2020 ; Geng et al, 2022b ; Cai et al, 2022 ). In the following section, we explore the potential mechanisms and application value of different EVs ( Figure 1 ).…”

Section: The Pathogenesis Of Poi and The Application Of Stem Cell-der...mentioning

confidence: 99%

“…There are round or oval membranous vesicles, which can be aggregated and distributed, and their membrane structure is clearly defined ( Vohra et al, 2020 ). hUCMSCs-EVs express the EVs-specific four-transmembrane protein markers CD9, CD63, CD81 and tumor susceptibility gene 101 protein (TSG101), heat shock protein70 (HSP70), and the multivesicular biosynthesis-related protein ALIX ( Sun et al, 2017 ; Yang et al, 2019 ; Zhang et al, 2020 ; Deng et al, 2021 ; Cai et al, 2022 ; Gao et al, 2022 ; Qu et al, 2022 ). In 2017, hUCMSCs- EVs were first described for application to POI by Sun et al (2017) .…”

Section: Human Umbilical Cord Mesenchymal Stem Cells-derived Evs (Huc...mentioning

confidence: 99%

Stem cell-derived extracellular vesicles: A novel and potential remedy for primary ovarian insufficiency

Geng

Guo²,

Li³

et al. 2023

Front. Cell Dev. Biol.

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Primary ovarian insufficiency (POI) is an essential cause of young female fertility loss. At present, there are many treatments for primary ovarian insufficiency, but due to the complexity of the pathogenesis of primary ovarian insufficiency, the efficacy still could not be satisfactory. Stem cell transplantation is a feasible intervention protocol for primary ovarian insufficiency. However, its wide application in the clinic is limited by some defects such as tumorigenic and controversial ethical issues. Stem cell-derived extracellular vesicles (EVs) represent an important mode of intercellular communication attracting increasing interest. It is well documented that stem cell-derived extracellular vesicles for primary ovarian insufficiency with exciting therapeutic effects. Studies have found that stem cell-derived extracellular vesicles could improve ovarian reserve, increase the growth of follicles, reduce follicle atresia, and restore hormone levels of FSH and E2. Its mechanisms include inhibiting ovarian granulosa cells (GCs) apoptosis, reactive oxygen species, and inflammatory response and promoting granulosa cells proliferation and angiogenesis. Thus, stem cell-derived extracellular vesicles are a promising and potential method for primary ovarian insufficiency patients. However, stem cell-derived extracellular vesicles are still a long way from clinical translation. This review will provide an overview of the role and the mechanisms of stem cell-derived extracellular vesicles in primary ovarian insufficiency, and further elaborate on the current challenges. It may suggest new directions for future research.

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HucMSCs-exosomes containing miR-21 promoted estrogen production in ovarian granulosa cells via LATS1-mediated phosphorylation of LOXL2 and YAP

Cited by 21 publications

References 31 publications

Human Umbilical Cord Mesenchymal Stem Cells Improve Premature Ovarian Failure through Cell Apoptosis of miR-100-5p/NOX4/NLRP3

Human Umbilical Cord Mesenchymal Stem Cells Improve Premature Ovarian Failure through Cell Apoptosis of miR-100-5p/NOX4/NLRP3

Bone marrow mesenchymal stem cells in premature ovarian failure: Mechanisms and prospects

Stem cell-derived extracellular vesicles: A novel and potential remedy for primary ovarian insufficiency

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