Micro<scp>RNA</scp>s downregulated following immune activation of rat testis

Parker, Mitchell I.; Palladino, Michael A.

doi:10.1111/aji.12673

Cited by 22 publications

(23 citation statements)

References 13 publications

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“…In addition, TLR stimulation elevates the synthesis of proinflammatory cytokines such as IL-1β and TNF (both of which showed elevated mRNA expression in our study) so perhaps TLR-dependent pathways and not NF-κB is the predominant activation pathway for HIF-1 in the testis. Recently we have also demonstrated that expression of a number of microRNAs in the testis are downregulated by LPS including miRNAs involved in regulating the NF-κB pathway [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of lipopolysaccharide-induced inflammation on hypoxia and inflammatory gene expression pathways of the rat testis

Palladino

Fasano

Patel

et al. 2018

Basic Clin. Androl.

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BackgroundBacterial infection and inflammation of the testis impairs fertility, yet an understanding of inflammatory responses of the testis is incomplete. We are interested in identifying gene pathways involved in the detection and clearance of infectious microbes in the male reproductive tract. In previous studies in our lab focused on hypoxia-responsive genes of the testis, preliminary experiments suggested that genes classically categorized as hypoxia genes are also activated during antimicrobial responses. The purpose of this study was to identify hypoxia and inflammatory gene pathways that contribute to antimicrobial protection of the testis and to consider possible cross-talk and interactions between these pathways. Inflammation was induced in Sprague-Dawley rats using P. aeruginosa or E. coli lipopolysaccharide (LPS). Levels of hypoxia-inducible factor-1 (HIF-1α) protein and nuclear factor kappa B (NF-κB) were measured, and hypoxia and inflammatory gene expression patterns in testis were analyzed by gene expression profiling using real-time quantitative PCR arrays.ResultsIn LPS-treated rats, HIF-1α protein increased with no change in Hif-1α mRNA. Western Blot analysis also demonstrated no change in NF-κB and inhibitory NFKB alpha (IκBα) protein levels following LPS treatment. Five hypoxia pathway genes (Angptl4, Egr1, Ier3, Pai1, and Glut1), and 11 inflammatory pathway genes (Ccl12, Cc13, Cd14, Cxcl10, Icam1, Il10, Il1b, Il6, Nfkbia, Tlr2, Tnf) up-regulated after 3 h of inflammation. Angptl4, Ccl12, Cc13, Cd14, Egr1, Nfkbia, Tlr2, and Tnf remained elevated at 6 h. Six genes were up-regulated at 6 h only (Bhlhe40, C3, Jak2, Nlrp3, Slc11a1, Tlr1). One gene (Tlr5) was down-regulated after 3 h and no genes at 6 h. Electrophoretic mobility shift assay results suggest a decrease in NF-κB binding activity following LPS treatment.ConclusionsTesticular HIF-1α is up-regulated following LPS-induced inflammation. In contrast to other tissues, in which HIF-1α is up-regulated through transcriptional activation via NF-κB, we conclude that HIF-1α in the testis is not up-regulated through an increase in Hif-1α mRNA or through NF-κB-dependent mechanisms. Hypoxia pathway genes and genes involved in Toll-like receptor (TLR) and cytokine-mediated signaling comprise major functional categories of up-regulated genes, demonstrating that both hypoxia and classic inflammatory pathways are involved in inflammatory responses of the testis.Electronic supplementary materialThe online version of this article (10.1186/s12610-018-0079-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Effects of lipopolysaccharide-induced inflammation on hypoxia and inflammatory gene expression pathways of the rat testis

Palladino

Fasano

Patel

et al. 2018

Basic Clin. Androl.

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“…let-7f-5p may prove to be a valid molecular biomarker for carcinoma. It is correlated with suppression of the target gene HMGA2 [85], and plays important roles in the maintenance of fertility [86], cell proliferation [87], and neuronal differentiation [88]. let-7f-5p also inhibits the porcine reproductive and respiratory syndrome virus by targeting MYH9 [89].…”

Section: Potential Functions Of Highly Expressed Mirnas In Biofluid Ementioning

confidence: 99%

High-throughput sequencing reveals biofluid exosomal miRNAs associated with immunity in pigs

Zhang

Luo

Xiong

et al. 2020

Bioscience, Biotechnology, and Biochemistry

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Large numbers of miRNAs are found in biofluid exosomes. We isolated~50-200 nm diameter exosomes from four types of porcine biofluid (urine, plasma, semen, and bile) using serial centrifugation and ultracentrifugation procedures. A total of 42.15 M raw data were generated from four small RNA libraries. This produced 40.17 M map-able sequences, of which we identified 204 conserved miRNAs, and 190 novel candidate miRNAs. Furthermore, we identified 34 miRNAs specifically expressed in only one library, all with well-characterized immunerelated functions. A set of five universally abundant miRNAs (miR-148a-3p, miR-21-5p, let-7f-5p, let-7i-5p, and miR-99a-5p) across all four biofluids was also found. Function enrichment analysis revealed that the target genes of the five ubiquitous miRNAs are primarily involved in immune and RNA metabolic processes. In summary, our findings suggest that porcine biofluid exosomes contain a large number of miRNAs, many of which may be crucial regulators of the immune system.

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“…Furthermore, miRNAs serve as crucial contributors of orchitis. For instance, it was previously revealed that multiple inflammation-associated miRNAs were inhibited in response to LPS exposure in murine testis models (Parker and Palladino 2017). Moreover, let-7, miR-17, and miR-449a exerted overlapping regulatory effects on male fertility.…”

Section: Introductionmentioning

confidence: 99%

CircRNA-9119 suppresses poly I:C induced inflammation in Leydig and Sertoli cells via TLR3 and RIG-I signal pathways

Qin

Lin

Xie

2019

Mol Med

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Background Circular RNAs (circRNAs) contribute to the epigenetic modulation of pathological and physiological conditions. The understanding of the impact of circRNAs on generation of testicular inflammatory reactions is insufficient. Methods Our research adopted a poly I:C-triggered testicular inflammation murine model and cell assays. Results Microarray data and quantitative evaluation revealed the elevation in the concentrations of Toll-like receptor 3 (TLR3), circRNA-9119, and retinoic acid inducible gene-I (RIG-I) and repression in the levels of miR-136 and miR-26a. Inhibition of circRNA-9119 expression impaired the inflammatory reactions in the separated Leydig and Sertoli cells subjected to poly I:C treatment. CircRNA-9119 suppressed the expression of miR-136 and miR-26a by acting as a microRNA sponge. miR-136 and miR-26a repressed the expression of RIG-I and TLR3 through the expected target region in Leydig and Sertoli cells in vitro. Inhibition of miR-136 and miR-26a expression, at least in part, restored the expression of inflammatory cytokines, which were inhibited upon circRNA-9119 expression silencing. Furthermore, the expression of circRNA-9119 was positively associated with RIG-I and TLR3 mRNA and protein levels. The expression of inflammatory genes triggered by poly I:C treatment was noticeably suppressed after RIG-I and TLR3 knockout. Conclusions Our results suggest that circRNA-9119 may serve as a competing endogenous RNA that insulated miR-136 and miR-26a and consequently defended RIG-I and TLR3 mRNAs against miR-26a/miR-136-mediated inhibition of testicular cells. Moreover, RIG-I and TLR3 contributed to the modulation of poly I:C-triggered inflammatory cytokine generation during orchitis in testicular cells. Electronic supplementary material The online version of this article (10.1186/s10020-019-0094-1) contains supplementary material, which is available to authorized users.

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MicroRNAs downregulated following immune activation of rat testis

Cited by 22 publications

References 13 publications

Effects of lipopolysaccharide-induced inflammation on hypoxia and inflammatory gene expression pathways of the rat testis

Effects of lipopolysaccharide-induced inflammation on hypoxia and inflammatory gene expression pathways of the rat testis

High-throughput sequencing reveals biofluid exosomal miRNAs associated with immunity in pigs

CircRNA-9119 suppresses poly I:C induced inflammation in Leydig and Sertoli cells via TLR3 and RIG-I signal pathways

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