scholarly journals Exosome-Derived microRNAs in Sertoli Cells Inhibit Spermatogonial Apoptosis

2021 ◽  
Author(s):  
Huihui Gao ◽  
Heran Cao ◽  
Tianqi Jin ◽  
Guofan Peng ◽  
Yining Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sertoli Cells ◽  
Target Gene ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Mapk Signaling ◽  
Seminiferous Tubules ◽  
Akt Signaling Pathway ◽  
Paracrine Factors ◽  
Regulated Expression

Abstract BackgroundSpermatogenesis is a highly complicated biological process that occurs in the epithelium of the seminiferous tubules. It is regulated by a complex network of endocrine and paracrine factors and juxtacrine testicular cross-talk . Sertoli cells (SCs) play a key role in spermatogenesis due to their production of trophic, differentiation and immune-modulating factors. However, many of the molecular pathways of SCs action remain controversial and unclear. Recently, research has focused on exosomes as an important mechanism of intercellular communication. ResultsW e found that the exosomes derived from SCs ( SC-Exos ) significantly inhibited the apoptosis of the primary spermatogonial stem cells (SSCs). Total of 1016 miRNAs in SCs and 556 miRNAs in SC-Exos were detected using microRNA (miRNA) high-throughput sequencing. Further, 294 miRNAs were differentially expressed between SCs and SC-Exos. Based on the GO and KEGG analyses, the target genes of 37 (high-expressed in exosomes and RPM>1000) selected miRNAs were involved in multiple biological pathw ays, including the MAPK signaling pathway and PI3K/AKT signaling pathway. And miR-10b is one of the top ten exosomes with relatively large enrichment of microRNA. In addition, the overexpression of miR-10b down-regulated expression of the target KLF4 to reduce spermatogonial apoptosis in SSCs or C18-4 cell line. ConclusionsThe study indicated a large number of small RNAs loaded in exosomes was secreted form the donor SCs to target spermatogonial regulated the apoptosis. And miR-10b inhibits the apoptosis of spermatogonia through the target gene KLF4.

Dysregulation of tRNA-derived small RNAs and their potential roles in lupus nephritis

Lupus ◽  
2021 ◽  
pp. 096120332110614
Author(s):  
Yan Liang ◽  
Ji Zhang ◽  
Wenxian Qiu ◽  
Bo Chen ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Signaling Pathway ◽  
Small Rnas ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Expression Profiles ◽  
Mapk Signaling ◽  
Pcr Analysis ◽  
Clinical Indicators ◽  
Qrt Pcr

Objective Lupus nephritis (LN) is a major end-organ complication of systemic lupus erythematosus (SLE), and the molecular mechanism of LN is not completely clear. Accumulating pieces of evidence indicate the potential vital role of tRNA-derived small RNAs (tsRNAs) in human diseases. Current study aimed to investigate the potential roles of tsRNAs in LN. Methods We herein employed high‐throughput sequencing to screen the expression profiles of tsRNAs in renal tissues of the LN and control groups. To validate the sequencing data, we performed quantitative real-time PCR (qRT-PCR) analysis. Correlational analysis of verified tsRNAs expression and clinical indicators was conducted using linear regression. The potential target genes were also predicted. The biological functions of tsRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results Our findings revealed that the expression profiles of tsRNAs were significantly altered in the kidney tissues from LN patients compared with control. Overall, 160 tsRNAs were significantly dysregulated in the LN group, of which 79 were upregulated, whereas 81 were downregulated. Subsequent qRT-PCR results confirmed the different expression of candidate tsRNAs. Correlation analysis results found that expression of verified tsRNAs were correlated to clinical indicators. The target prediction results revealed that verified tsRNAs might act on 712 target genes. Further bioinformatics analysis uncovered tsRNAs might participate in the pathogenesis of LN through several associated pathways, including cell adhesion molecules, MAPK signaling pathway, PI3K-Akt signaling pathway and B cell receptor signaling pathway. Conclusion This study provides a novel insight for studying the mechanism of LN.

scholarly journals miR-499 promotes immature porcine Sertoli cell growth through the PI3K/AKT pathway by targeting the PTEN gene

Reproduction ◽  
2020 ◽  
Vol 159 (2) ◽  
pp. 145-157 ◽  
Author(s):  
Hu Gao ◽  
Bin Chen ◽  
Hui Luo ◽  
Bo Weng ◽  
Xiangwei Tang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Pten Gene ◽  
Seminiferous Tubules ◽  
Akt Signaling Pathway

Sertoli cells are indispensable for normal spermatogenesis, and increasing evidence has shown that miRNAs participate in the regulation of Sertoli cell growth. However, the functions and regulatory mechanisms of miRNAs in Sertoli cells of domestic animals have not been fully investigated. In the present study, we mainly investigated the regulatory roles of miR-499 in immature porcine Sertoli cells. The results showed that miR-499 was mainly located in the basement section of seminiferous tubules of prepubertal porcine testicular tissue. Overexpression of miR-499 promoted cell proliferation and inhibited apoptosis, whereas miR-499 inhibition resulted in the opposite effect. The PTEN gene was directly targeted by miR-499, and the expression of mRNA and protein was also negatively regulated by miR-499 in immature porcine Sertoli cells. siRNA-induced PTEN knockdown resulted in a similar effect as an overexpression of miR-499 and abolished the effects of miR-499 inhibition on immature porcine Sertoli cells. Moreover, both miR-499 overexpression and the PTEN knockdown activated the PI3K/AKT signaling pathway, whereas inhibition of the PI3K/AKT signaling pathway caused immature porcine Sertoli cell apoptosis and inhibited cell proliferation. Overall, miR-499 promotes proliferation and inhibits apoptosis in immature porcine Sertoli cells through the PI3K/AKT pathway by targeting the PTEN gene. This study provides novel insights into the effects of miR-499 in spermatogenesis through the regulation of immature Sertoli cell proliferation and apoptosis.

Identification and Functional Analysis of Serum Specific MiRNAs in Patients with Recurrent Aphthous Somatitis of Excess-heat or Yin-deficiency Syndrome

2019 ◽  
Author(s):  
Jie Bao ◽  
Zhengyang Zhu ◽  
Xizhao Zhang ◽  
Lin Huang ◽  
Li Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Kegg Pathway ◽  
Deficiency Syndrome ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Excess Heat ◽  
Yin Deficiency ◽  
Heat Syndrome

Abstract Background. MiRNAs has become an important regulator in many processes. The purpose of our study is to screen the key serum miRNAs of different syndrome of recurrent aphthous stomatitis (RAS), to find new biomarkers for the diagnosis of RAS and to further explore their role in the pathogenesis of RAS.Method. Serum samples were collected from patients meeting the RAS diagnostic criteria of excess-heat or yin-deficiency syndrome and healthy individuals. Core miRNAs were then identified under miRNA microarray analyses. Target prediction and bioinformatic analyses were carried out and gene-pathway-networks were visualized to better understand the relationship between different genes and pathways.Result. (1) 90 individuals meeting the inclusion criteria were collected in this study, of which 30 were normal control, 30 were patients of excess-heat syndrome and the rest were patients of yin-deficiency syndrome. Among them, 9 miRNAs were screened out in excess-heat syndrome group, with 1 upregulated and 8 downregulated. And four random miRNAs (hsa-miR-20b-5p, hsa-miR-122-5p, hsa-miR-483-5p and hsa-miR-3197) were validated by real-time PCR method. 14 miRNAs were screened out in yin-deficiency syndrome group (7 upregulated and 7 downregulated). And hsa-miR-17-5p, hsa-miR-106-5p and hsa-miR-20b-5p were validated. (2) A total of 4776 target genes were identified for the validated 9 miRNAs in excess-heat syndrome group. These targets were enriched in GO categories including nervous system development, homophilic cell adhesion via plasma membrane adhesion molecules, and calcium ion binding and KEGG pathway such as proteoglycans in cancer, P13K-AKT signaling pathway and Calcium signaling pathway. 10172 target genes were identified for the validated 14 miRNAs in yin-deficiency syndrome group. The enriched GO categories included protein binding, positive regulation of transcription from RNA polymerase II promoter and membrane and enriched KEGG pathway included pathways in cancer, MAPK signaling pathway and Ras signaling pathway .Conclusion. Hsa-miR-20b-5p in patients with RAS could act as the novel biomarker for clinical diagnosis of the disease. It is upregulated in RAS patients of excess-heat syndrome while downregulated in patients of yin-deficiency syndrome. The PI3K-Akt signaling pathway and MAPK signaling pathway and related target genes may provide new insights into the molecular mechanisms of excess-heat syndrome and yin-deficiency syndrome RAS, respectively.

scholarly journals Analysis of the microRNA Expression Profile of Bovine Monocyte-derived Macrophages Infected with Mycobacterium avium subsp. Paratuberculosis Reveals that miR-150 Suppresses Cell Apoptosis by Targeting PDCD4

2019 ◽  
Vol 20 (11) ◽  
pp. 2708 ◽  
Author(s):  
Zi Wang ◽  
Ling Cong Kong ◽  
Bo Yan Jia ◽  
Jing Rui Chen ◽  
Yang Dong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Mapk Signaling ◽  
Johne's Disease ◽  
Johne’S Disease ◽  
Luciferase Reporter ◽  
Nf Kappa B ◽  
Mycobacterium Avium Subsp Paratuberculosis

M. avium subsp. paratuberculosis (MAP) is the causative pathogen of Johne’s disease, a chronic granulomatous enteritis that principally affects ruminants and can survive, proliferate and disseminate in macrophages. MicroRNAs (miRNAs) are important regulators of gene expression and can impact the processes of cells. To investigate the role of miRNAs in monocyte-derived macrophages (MDMs) during MAP infection, we used high-throughput sequencing technology to analyze small RNA libraries of MAP-infected and control MDMs. The results showed that a total of 21 miRNAs were differentially expressed in MDMs after MAP infection, and 8864 target genes were predicted. A functional analysis showed that the target genes were mainly involved in the MAPK signaling pathway, Toll-like receptor signaling pathway, NF-kappa B signaling pathway and apoptosis. In addition, using a dual-luciferase reporter assay, flow cytometry, and a small interfering (si)RNA knockdown assay, the role of miR-150 in regulating macrophage apoptosis by targeting the programmed cell death protein-4 (PDCD4) was demonstrated. These results provide an experimental basis to reveal the regulatory mechanism of MAP infection and suggest the potential of miRNAs as biomarkers for the diagnosis of Johne’s disease in bovines.

scholarly journals Identification and Functional Analysis of Serum Specific MiRNAs in Recurrent Aphthous Somatitis Patients With Excess-heat or Yin-deficiency

2020 ◽  
Author(s):  
Jie Bao ◽  
Zhengyang Zhu ◽  
Xizhao Zhang ◽  
Lin Huang ◽  
Li Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Deficiency Syndrome ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Akt Signaling Pathway ◽  
Excess Heat ◽  
Yin Deficiency ◽  
Heat Syndrome

Abstract Background:To identity key miRNAs as signatures for recurrent aphthous stomatitis(RAS)with Excess-heat or Yin-deficiency bymiRNA microarrays. Method: Serum samples were collected from patients meeting the RAS diagnostic criteria of excess-heat oryin-deficiencysyndrome and healthy individuals. CoremicroRNAs (miRNAs) were then identified under miRNA microarray analyses. Target prediction and bioinformatic analyses were carried out andgene-pathway-networks werevisualized to better understand the relationship between differentgenes and pathways.Result:(1) 90 individuals meeting the inclusion criteria were collected in this study, of which 30 were normal control, 30 were patients of excess-heat syndrome and the rest were patients ofyin-deficiency syndrome. Among them, 9 miRNAs werescreened out in excess-heat syndrome group, with 1 upregulated and 8 downregulated. And four randommiRNAs(hsa-miR-20b-5p, hsa-miR-122-5p, hsa-miR-483-5p and hsa-miR-3197) were validatedby real-time PCR method. 14 miRNAs werescreened out in yin-deficiency syndrome group(7 upregulated and 7 downregulated). And hsa-miR-17-5p, hsa-miR-106-5p and hsa-miR-20b-5p were validated. (2)A total of 4776 target genes were identified for the validated 9 miRNAs in excess-heat syndrome group.These targets were enriched inGO categories including nervous system development, homophilic cell adhesion via plasma membrane adhesion molecules, and calcium ion binding and KEGG pathway such as proteoglycans in cancer, P13K-AKT signaling pathway and Calcium signaling pathway. 10172 target genes were identified for the validated 14 miRNAs in yin-deficiency syndrome group. The enrichedGO categories included protein binding, positive regulation of transcription from RNA polymerase II promoter and membrane andenrichedKEGG pathway included pathways in cancer, MAPK signaling pathway and Ras signaling pathway.Conclusion:Hsa-miR-20b-5p in patients with RAS could act as the novel target for syndromeclassification of the disease. It is upregulated in RAS patients with excess-heat syndrome while downregulated in patients with yin-deficiency syndrome. The PI3K-Akt signaling pathway and MAPK signaling pathway and related target genes may provide new insights into the molecular mechanisms of RAS with excess-heat syndrome or yin-deficiency syndrome, respectively.

scholarly journals Influence of PM2.5 on spermatogenesis dysfunction via the reactive-oxygen-species-mediated Mitogen-activated-protein-kinase signaling pathway

2019 ◽  
Vol 6 (4) ◽  
pp. 77-79
Author(s):  
Ruangrong Cheepsattayakorn
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Human Sperm ◽  
Mapk Signaling ◽  
Autoimmune Response ◽  
Sperm Chromatin ◽  
Seminiferous Tubules ◽  
Oxygen Species ◽  
Mitogen Activated Protein

Approximately 15 % of the world‘s couples confront childless, and about 50 % of them are due to male reproductive disorders. Several previous studies demonstrated that PM2.5 particles has been consistently associated with critical human sperm reduction and impairment of human sperm chromatin and DNA from traffic exhaust pollution. Blood-testis barrier (BTB), a critically physical barrier between the seminiferous tubules and the blood vessels prevents sperm antigens from entering the blood circulation and facilitating and initiating an autoimmune response that contributing to spermatogenesis interference. Reactive oxygen species (ROS) are involved in the redox-sensitive signal transduction factors activation, such as Jun NH2-terminal kinase (JNK), p 38, extracellular signal-regulated kinase (ERK), and mitogen-activated protein kinases (MAPK) that critically influence BTB disruption. After PM2.5 exposure, there are decreased superoxide dismutase (SOD) expression, increased malondialdehyde (MDA) expression, increased nuclear factor erythroid 2-related factor 2 (Nrf-2) expression, increased expression of the four junctional proteins (β-catenin, Cx43, occludin, zonula occludens-1 (ZO-1)), thus improve sperm quality and quantity. PM2.5 particles markedly induce increasing phosphorylation of MAPKs via the ROS-mediated MAPK signaling pathway that causes BTB disruption, but this effect is lesser in the vitamins C and E intervention as well as increasing cleaved caspase-3 expression and the Bcl-2/Bax ratio. In conclusion, combined therapeutic administration of vitamins C and E can maintain the BTB integrity, reduce oxidative stress and cell apoptosis, and prevent toxic effects.

Analysis of MicroRNA Transcriptomes Insights into the miR-148a-3p Inducer of Rumen Development in Goats

2020 ◽  
Author(s):  
Tao Zhong ◽  
Cheng Wang ◽  
Jiangtao Hu ◽  
Xiaoyong Chen ◽  
Lili Niu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Genetic Regulation ◽  
Mapk Signaling ◽  
Regulation Mechanism ◽  
Ras Signaling ◽  
Genome Wide ◽  
A Genome ◽  
Differentially Expressed Mirnas ◽  
And Function

Abstract Background: Rumen is an important digestive organ of ruminant. From fetal to adult stage, the morphology, structure and function of rumen have changed significantly. But the intrinsic genetic regulation is still limited. We previously reported a genome-wide expression profile of miRNAs in prenatal goat rumens. In the present study, we rejoined analyzed the transcriptomes of rumen miRNAs during prenatal (E60 and E135) and postnatal (D30 and D150) stages.Results: A total of 66 differentially expressed miRNAs (DEMs) were identified in the rumen tissues from D30 and D150 goats. Of these, 17 DEMs were consistently highly expressed in the rumens at the preweaning stages (E60, E135 and D30), while down-regulated at D150. Noteworthy, annotation analysis revealed that the target genes regulated by the DEMs were mainly enriched in MAPK signaling pathway, Jak-STAT signaling pathway and Ras signaling pathway. Interestingly, the expression of miR-148a-3p was significantly high in the embryonic stage and down-regulated at D150. The potential binding sites between miR-148a-3p and QKI were predicted by the TargetScan and verified by the dual luciferase report assay. The co-localization of miR-148a-3p and QKI was observed not in intestinal tracts but in rumen tissues by in situ hybridization. Moreover, the expression of miR-148a-3p in the epithelium was significantly higher than that in the other layers, suggesting that miR-148a-3p involve in the development of rumen epithelial cells by targeting QKI. Subsequently, miR-148a-3p inhibitor was found to induce the proliferation of GES-1 cells.Conclusions: Taken together, these results identified the DEMs involved in the development of rumen and provided an insight into the regulation mechanism of goat rumens during development.

scholarly journals The Expression of microRNA in Adult Rat Heart with Isoproterenol-Induced Cardiac Hypertrophy

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1173 ◽  
Author(s):  
Mailin Gan ◽  
Shunhua Zhang ◽  
Yuan Fan ◽  
Ya Tan ◽  
Zhixian Guo ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Natriuretic Peptide ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Pathological Condition ◽  
Wnt Signaling Pathway ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter

Cardiac hypertrophy is a common pathological condition and an independent risk factor that triggers cardiovascular morbidity. As an important epigenetic regulator, miRNA is widely involved in many biological processes. In this study, miRNAs expressed in rat hearts that underwent isoprenaline-induced cardiac hypertrophy were identified using high-throughput sequencing, and functional verification of typical miRNAs was performed using rat primary cardiomyocytes. A total of 623 miRNAs were identified, of which 33 were specifically expressed in cardiac hypertrophy rats. The enriched pathways of target genes of differentially expressed miRNAs included the FoxO signaling pathway, dopaminergic synapse, Wnt signaling pathway, MAPK (mitogen-activated protein kinase) signaling pathway, and Hippo signaling pathway. Subsequently, miR-144 was the most differentially expressed miRNA and was subsequently selected for in vitro validation. Inhibition of miR-144 expression in primary myocardial cells caused up-regulation of cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The dual luciferase reporter system showed that ANP may be a target gene of miR-144. Long non-coding RNA myocardial infarction associated transcript (LncMIAT) is closely related to heart disease, and here, we were the first to discover that LncMIAT may act as an miR-144 sponge in isoproterenol-induced cardiac hypertrophy. Taken together, these results enriched the understanding of miRNA in regulating cardiac hypertrophy and provided a reference for preventing and treating cardiac hypertrophy.

scholarly journals High-throughput sequencing reveals differential expression of miRNAs in prehierarchal follicles of laying and brooding geese

2016 ◽  
Vol 48 (7) ◽  
pp. 455-463 ◽  
Author(s):  
Jing Yu ◽  
Ke He ◽  
Ting Ren ◽  
Yaping Lou ◽  
Ayong Zhao
Keyword(s):  
Signaling Pathway ◽  
High Throughput ◽  
Egg Production ◽  
High Throughput Sequencing ◽  
Wnt Signaling Pathway ◽  
Mapk Signaling ◽  
Follicle Development ◽  
Large White ◽  
Functional Involvement ◽  
Development Levels

Broodiness is the primary factor influencing egg production in geese, in which several genes and miRNAs participate. Detailed spatiotemporal profiles of miRNAs encompassing follicle development levels, however, are lacking. In this study, we collected preovulatory follicles (classified as small white follicles, large white follicles, and small yellow follicles) from brooding and laying geese and aimed to analyze microRNA (miRNA or miR) during folliculogenesis. High-throughput sequencing and bioinformatics analysis were used to identify the miRNAs involved in follicle development. The let7 family, miR-10 family, and miR-143 family were abundant in these libraries, and they have been suggested to play a housekeeping role during folliculogenesis. Joint comparisons revealed 23 upregulated and 21 downregulated miRNAs (in at least two comparisons of follicles during brooding and laying, P < 0.1) in the laying stage. Unlike reproduction pathways reported for ovaries, GO and KEGG analysis suggested pathways for cell apoptosis and proliferation, such as the regulation of actin cytoskeleton, endocytosis, axon guidance, pathways in cancer, tight junctions, focal adhesion, the MAPK signaling pathway, cytokine-cytokine receptor interactions, and the Wnt signaling pathway in folliculogenesis. This study revealed the miRNAs that were directly involved in follicular atresia, and our results added to the understanding of the functional involvement of miRNAs during specific stages of follicle development.

scholarly journals Integrated analysis of miRNA and mRNA expression profiles in testes of Duroc and Meishan boars

2019 ◽  
Author(s):  
Haisheng Ding ◽  
Min Liu ◽  
Changfan Zhou ◽  
Xiangbin You ◽  
Tao Su ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Target Genes ◽  
Expression Profiles ◽  
Male Gamete ◽  
Mirna Expression Profile ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Testis Development ◽  
Differentially Expressed Mirnas

Abstract Background: MicroRNAs (miRNAs) are small non-coding RNAs playing vital roles in regulating posttranscriptional gene expression. Elucidating the expression regulation of miRNAs underlying pig testis development will contribute to a better understanding of boar fertility and spermatogenesis. Results: In this study, miRNA expression profile was investigated in testes of Duroc and Meishan boars at 20, 75, and 270 days of age by high-throughput sequencing. Forty-five differentially expressed miRNAs were identified from testes of Duroc and Meishan boars before and after puberty. Integrated analysis of miRNA and mRNA profiles predicted many miRNA-mRNA pairs. Gene ontology and biological pathway analyses revealed that predicted target genes of ssc-mir-423-5p, ssc-mir-34c, ssc-mir-107, ssc-165 mir-196b-5p, ssc-mir-92a, ssc-mir-320, ssc-mir-10a-5p, and ssc-mir-181b were involved in sexual reproduction, male gamete generation, and spermatogenesis, and GnRH, Wnt, and MAPK signaling pathway. Four significantly differentially expressed miRNAs and their predicted target genes were validated by quantitative real-time polymerase chain reaction, and phospholipase C beta 1 ( PLCβ1) gene was verified to be a target of ssc-mir-423-5p . Conclusions: This study provides an insight into the functional roles of miRNAs in testis development and spermatogenesis and offers useful resources for understanding differences in sexual function development caused by the change in miRNAs expression between Duroc and Meishan boars.

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