Conjunctival MicroRNA Expression in Inflammatory Trachomatous Scarring

Derrick, Tamsyn; Roberts, Chrissy h.; Rajasekhar, Megha; Burr, Sarah E.; Joof, Hassan; Makalo, Pateh; Bailey, Robin L.; Mabey, David; Burton, Matthew J.; Holland, Martin J.

doi:10.1371/journal.pntd.0002117

Cited by 45 publications

(49 citation statements)

References 38 publications

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“…However, it would be interesting to determine if these miRNA responses persist in Nigg A -infected mice at later time points. Moreover, upregulation of profibrotic miR-142-3p and miRNA 147 were also observed with Nigg V infection, consistent with the inflammatory C. trachomatis scarring model (28). Nigg V infection results in a higher bacterial load; thus, it is possible that increased inflammatory responses and miRNA expression are due to a higher replicative capacity of the chlamydiae.…”

Section: Discussionsupporting

confidence: 74%

“…miRNAs and Chlamydial Pathogenesis Infection and Immunity fibrosis and epithelial cell differentiation in human samples of chlamydial conjunctival inflammatory scarring (28). The study indicated that significant changes in miRNA expression are associated with the late-stage disease process.…”

Section: Discussionmentioning

confidence: 89%

“…3 and 4). miRNAs have been shown to be differentially expressed during chlamydial infections (3,28,(43)(44)(45)(46). To determine if infection with Nigg A or Nigg V has an impact on miRNA expression in mice, cervices infected for 4 days were subjected to microarray analyses.…”

Section: Discussionmentioning

confidence: 99%

“…For example, a differential expression profile of circulating (serum) miRNA has been observed during hepatitis C virus infection (24,25) and during Helicobacter, Mycobacterium, Salmonella, and Listeria infections (9,26,27). In addition, differential miRNA expression was associated with inflammatory scarring in patients with ocular Chlamydia trachomatis infection (28). Furthermore, during C. trachomatis serovar L2 infection in a mouse model, miRNAs were shown to be involved in controlling epithelial mesenchymal transition (EMT), fibrosis, and tumorigenesis.…”

mentioning

confidence: 99%

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MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice

et al. 2017

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Not all women infected with chlamydiae develop upper genital tract disease, but the reason(s) for this remains undefined. Host genetics and hormonal changes associated with the menstrual cycle are possible explanations for variable infection outcomes. It is also possible that disease severity depends on the virulence of the chlamydial inoculum. It is likely that the inoculum contains multiple genetic variants, differing in virulence. If the virulent variants dominate, then the individual is more likely to develop severe disease. Based on our previous studies, we hypothesized that the relative degree of virulence of a chlamydial population dictates the microRNA (miRNA) expression profile of the host, which, in turn, through regulation of the host inflammatory response, determines disease severity. Thus, we infected C57BL/6 mice with two populations of Chlamydia muridarum, each comprised of multiple genetic variants and differing in virulence: an attenuated strain (Nigg A ) and a virulent strain (Nigg V ). Nigg A and Nigg V elicited upper tract pathology in 54% and 91% of mice, respectively. miRNA expression analysis in Nigg V -infected mice showed significant downregulation of miRNAs involved in dampening fibrosis (miR-200b, miR-200b-5p, and 200b-3p miR-200a-3p) and in transcriptional regulation of cytokine responses (miR-148a-3p, miR-152-3p, miR-132, and miR-212) and upregulation of profibrotic miRNAs (miR-142, and miR-147). Downregulated miRNAs were associated with increased expression of interleukin 8 (IL-8), CXCL2, IL-1␤, tumor necrosis factor alpha (TNF-␣), and IL-6. Infection with Nigg V but not Nigg A led to decreased expression of Dicer and Ago 2, suggesting that Nigg V interaction with host cells inhibits expression of the miRNA biogenesis machinery, leading to increased cytokine expression and pathology.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice

et al. 2017

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“…16 In humans, microRNAs have been implicated in various diseases, 11,[22][23][24] including neovascularization 25 and fibrosis. However, the involvement of microRNAs in ocular surface fibrosis have been limited to descriptive studies of microRNA levels in diseases, 26 or induction by laser, 27 exogenous growth factor 28,29 or immunosuppressive drugs 30,31 in non-disease derived cultured ocular surface fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-215 Regulates Fibroblast Function: Insights from a Human Fibrotic Disease

Lan

Chen

Tong³

2015

Cell Cycle

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MicroRNAs are implicated in the regulation of gene expression via various mechanisms in health and disease, including fibrotic processes. Pterygium is an ocular surface condition characterized by abnormal fibroblast proliferation and matrix deposition. We aimed to investigate the role of microRNAs in pterygium and understand the relevant cellular and molecular mechanisms. To achieve this objective, a combination of approaches using surgically excised paired human pterygium and conjunctival tissues as well as cultured primary fibroblast cells from tissue explants were evaluated. Fibroblast dysfunction has been shown to play a central role in pterygium pathology. Here we show that miR-215, among a few others, was down-regulated (2-fold) in pterygium compared to control, and this was consistent in microarray, real-time PCR and fluorescent in-situ hybridization. The effects of increased miR-215 were investigated by adding exogenous miR-215 to fibroblasts, and this showed a decrease in cell proliferation but no significant apoptosis compared to control. Further cell cycle analysis showed that miR-215 depressed progression of cells at G1/S as well as G2/M. A few cell cycle related transcripts were downregulated (2.2-4.5-fold) on addition of miR-215: Mcm3, Dicer1, Cdc25A, Ick, Trip13 and Mcm10. Theoretic binding energies were used to predict miR-215 binding targets and luciferase reporter studies confirmed Mcm10 and Cdc25A as direct targets. In summary, mir-215 could play a role in inhibiting fibroblast proliferation in ocular surface conjunctiva. Dampening of this mir-215 could result in increased fibroblast cell cycling and proliferation, with possibly increased fibroblastic production of matrix, inducing pterygium formation.

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MicroRNA expressions associated with eosinophilic meningitis caused by Angiostrongylus cantonensis infection in a mouse model

Liao

Zeng

et al. 2014

Eur J Clin Microbiol Infect Dis

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Angiostrongylus cantonensis (A. cantonensis) infection is the major cause of eosinophilic meningitis (EM). Severe cases or infant and child cases have poor prognosis. MicroRNAs (miRNAs) play important roles in inflammation; however, little is known about the roles in brain inflammation caused by A. cantonensis. In this study, Illumina deep sequencing and bioinformatics were used to determine the abundance and differential expression of miRNAs in the brain tissues of a mouse model. A total of 648 conserved miRNAs were identified, 157 of which were significantly differentially expressed between infected mice and normal mice. The five most fold-changed miRNAs were miR-511-5p, miR-511-3p, miR-223-3p, miR-155-5p and miR-206-3p. These expressions of miR-511, miR-223, miR-155, miR-206, miR-142 and miR-21a were validated by quantitative reverse transcription polymerase chain reaction (RT-PCR). The analysis of these miRNAs showed that miR-511-3p was more abundant than the miR-511-5p strand, and increased to a peak in 21 days after A. cantonensis infection, miR-223 might be a potential indicator of disease severity and the upregulation of miR-155-5p after stimulation with the somatic antigen of phase IV A. cantonensis implied its involvement in the central nervous system (CNS) inflammation induced by A. cantonensis infection. These observations suggest that miRNAs may play important roles in the regulation of EM caused by A. cantonensis infection.

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Conjunctival MicroRNA Expression in Inflammatory Trachomatous Scarring

Cited by 45 publications

References 38 publications

MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice

MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice

MicroRNA-215 Regulates Fibroblast Function: Insights from a Human Fibrotic Disease

MicroRNA expressions associated with eosinophilic meningitis caused by Angiostrongylus cantonensis infection in a mouse model

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