Serum and Urinary Cell–free MiR-146a and MiR-155 in Patients with Systemic Lupus Erythematosus

Wang, Gang; Tam, Lai‐Shan; Li, Edmund Kwok-Ming; Kwan, Bonnie Ching‐Ha; Chow, Kai‐Ming; Luk, Cathy Choi-Wan; Li, Philip Kam-Tao; Szeto, Cheuk‐Chun

doi:10.3899/jrheum.100308

Cited by 180 publications

(153 citation statements)

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“…Systemic lupus erythematosus (SLE) is another autoimmune disorder reported to display deregulated levels of certain miRNAs, including miR-31 and again miR-146a and miR-155, which are reduced in SLE patients compared to controls [101,102]. Interestingly, miR-146a expression negatively correlated with type I IFN expression, and ectopic delivery of miR-146a in PBMCs from the SLE patients resulted in the reduction of the mRNA levels of IFN-inducible genes [102].…”

Section: Inflammatory Pathology Associated With Dysregulated Mirna-cymentioning

confidence: 99%

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Cross‐regulation between cytokine and microRNA pathways in T cells

et al. 2015

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microRNA (miRNA) mediated regulation of protein expression has emerged as an important mechanism in T-cell physiology, from development and survival to activation, proliferation, and differentiation. One of the major classes of proteins involved in these processes are cytokines, which are both key input signals and major products of T-cell function. Here, we summarize the current data on the molecular cross-talk between cytokines and miRNAs: how cytokines regulate miRNA expression, and how specific miRNAs control cytokine production in T cells. We also describe the inflammatory consequences of deregulating the miRNA/cytokine axis in mice and humans. We believe this topical area will have key implications for immune modulation and treatment of autoimmune pathology. Keywords:Cytokines r Inflammation r miRNA r T cells microRNAs as regulators of protein expressionBiological processes require the integration of environmental stimuli at the level of gene expression. The robustness of genetic networks depends on the distinction between physiological responses (to particular cues) and biological "noise" (stochastic variations), which can be achieved, for example, by establishing feed-forward transcriptional loops. Over the past two decades, a new mechanism that interacts with transcriptional loops and sets additional thresholds, which enable cells to filter physiological signals from noise has emerged; this mechanism regulates gene expression at the posttranscriptional level and relies on microRNAs (miRNAs; reviewed in [1]). These are an abundant class of evolutionarily conserved small noncoding (untranslated) RNA species that control target mRNA stability, degradation, and translation, thus affecting the majority of mammalian genes [2].Correspondence: Dr. Anita Q. Gomes e-mail: anitagomes@medicina.ulisboa.ptIn the conventional miRNA biogenesis pathway, RNA polymerase II transcribed pri-miRNAs are processed by the nuclear RNase III enzyme Drosha (complexed with DGCR8) to generate 60-70 nt stem-loop intermediates, the pre-miRNAs, that are further processed into 19-24mers in the cytoplasm by another key RNase III, Dicer. Mature miRNAs are then incorporated into RNAinduced silencing complexes, whose core components are proteins of the Argonaute family (Ago1-4), which use the 5 end (nucleotides 2-8) "seed sequence" of the miRNA to recognize complementary mRNA transcripts (mostly in their 3 untranslated region) for deadenylation or inhibition of translation, ultimately resulting in mRNA decapping and decay (reviewed in [3,4]).Unique spatial and temporal expression patterns in distinct hematopoietic cell lineages are suggestive of multiple roles for miRNAs in hematopoiesis, self-tolerance, and in immune responses, which have been explored over the past decade (reviewed in [5,6]). Over a 100 different miRNAs have been shown to be expressed by cells of the immune system, where * These authors contributed equally to this work as first authors. * * These authors contributed equally to this work as last authors.C 2015 WILEY-VCH Ve...

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Section: Inflammatory Pathology Associated With Dysregulated Mirna-cymentioning

confidence: 99%

“…Interestingly, miR-146a expression negatively correlated with type I IFN expression, and ectopic delivery of miR-146a in PBMCs from the SLE patients resulted in the reduction of the mRNA levels of IFN-inducible genes [102].…”

Section: Inflammatory Pathology Associated With Dysregulated Mirna-cymentioning

confidence: 99%

Cross‐regulation between cytokine and microRNA pathways in T cells

et al. 2015

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“…Moreover, miR-30 family (21,22) and miR-21 (23,24) were conserved expression in the kidneys of various species and are known to be involved in kidney disease. miR-155 (16,25) and miR-146a (25,26) were associated with immune response and their levels were altered in patients with kidney disease. The 25 miRNAs conserved expression in the kidneys (Supplemental Table 7) and 10 related with inflammation (Supplemental Table 8) were also selected as candidates.…”

Section: Identification Of Candidate Mirnasmentioning

confidence: 99%

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Zhang

Chen

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives This study aimed to identify urinary microRNAs (miRNAs) as biomarkers for FSGS disease activity.Design, setting, participants, & measurements Candidate urinary miRNAs were identified in pooled urine samples from patients with active FSGS (FSGS-A) and FSGS in remission (FSGS-CR), and were then validated using individual samples. Their levels were compared both under different treatment responses in a prospective study of FSGS and in patients with different membranous nephropathy (MN) and diabetic nephropathy (DN) disease activity. The prediction of these miRNAs for treatment responses was further analyzed in both retrospective and prospective cohorts of patients with FSGS.Results All 54 miRNAs were included as candidate biomarkers, including those with high levels in patients with FSGS-A (n=9) under the TaqMan Low Density Array as well as those with conserved expression in kidneys and involved in immune response. TaqMan probe-based quantitative RT-PCR confirmed the higher levels of four miRNAs in patients with FSGS-A in two independent cohorts (n=18 and n=80). Urinary miR-196a, miR-30a-5p, and miR-490 discriminated FSGS-A from FSGS-CR, with an area under the curve of $0.80. After steroid treatment, their levels were lower in steroid-responsive patients with FSGS (all P,0.001), but were unchanged in steroid-resistant patients. The levels of miRNAs were similar between active MN and MN in remission as well as active DN and incipient DN (all P.0.05). Urinary miR-30a-5p marginally predicted the response to steroid treatment in patients with FSGS-A, with an area under the curve of 0.63 (P=0.03). ConclusionsThe levels of urinary miR-196a, miR-30a-5p, and miR-490 are associated with FSGS disease activity.

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“…Experimental data were treated as 50-Ct for the subsequent statistical analysis, as described previously. 28 Protein Preparation and Western Blotting Protease inhibitors (Roche, Shanghai, China) were used during the isolation process. Protein from part of the right lung and from PASMCs (n ¼ 5 each group) was isolated using the proteoJET Mammalian Cell Lysis Reagent (Fermentas).…”

Section: Measurement Of Mirs and Mrnas In Lung Tissue Andmentioning

confidence: 99%

MicroRNA-206 is involved in hypoxia-induced pulmonary hypertension through targeting of the HIF-1α/Fhl-1 pathway

Yue

Guan

Wang

et al. 2013

Laboratory Investigation

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Hypoxia-induced pulmonary hypertension (PH), which is characterized by vasoconstriction and subsequent structural remodeling of blood vessels, is an important event in chronic obstructive pulmonary disease patients and in people living at high altitudes. Hypoxia-inducible factor-1a (HIF-1a) and its regulator four-and-a-half LIM (Lin-11, Isl-1 and Mec-3) domain 1 (Fhl-1) have important roles in hypoxia-induced PH. is critical for myogenesis and related diseases; however, the role of miR-206 in hypoxia-induced PH is unknown. miR-206 expression was evaluated in a hypoxic rat model and in cultured hypoxic pulmonary artery smooth muscle cells (PASMCs) using real-time quantitative PCR (RT-qPCR). HIF-1a and Fhl-1 expression were evaluated using RT-qPCR, western blotting, immunohistochemistry and immunofluorescence. The function of miR-206 was assessed by transfecting miR-206 mimics and inhibitors. Dualluciferase reporter gene assays and western blotting were performed to validate the target genes of miR-206. siRNA targeted against Fhl-1 was used to investigate the effect of Fhl-1 on miR-206. Flow cytometry was used to detect the cell cycle phase distribution in each group of PASMCs. Significant downregulation of miR-206 in hypoxic lung tissue and PASMCs was identified, whereas HIF-1a and Fhl-1 were upregulated in these samples. The expression of miR-206 in the serum was different from that in the lung tissue. Transfection of pre-miR miR-206 in hypoxic conditions led to increased expression of HIF-1a and Fhl-1 rather than abolishing hypoxia-induced HIF-1a and Fhl-1, as was expected, and promoted the entry of cells into the S phase and enhanced PASMC proliferation. Fhl-1-targeted siRNA in PASMC prevented cell proliferation and led to an increased proportion of cells in the G1 phase without altering miR-206 expression. Bioinformatic analysis and dual-luciferase reporter gene assays revealed direct evidence for miR-206 targeting of HIF-1a. In conclusion, hypoxia-induced downregulation of miR-206 promotes PH by targeting the HIF-1a/Fhl-1 pathway in PASMCs. miR-206 could be a triggering factor of early stage of hypoxia-induced PH. Hypoxia-induced pulmonary hypertension (PH) is a serious disorder characterized by pulmonary vasoconstriction and enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) that lead to structural remodeling of blood vessel walls. PH is a common clinical manifestation of chronic obstructive pulmonary disease (COPD) and in people who live at high altitude. 1 Hypoxia-inducible factor-1a (HIF-1a) has a key role in the pathophysiology of hypoxia-induced PH.The four-and-a-half LIM domain 1 (Fhl-1) protein, a member of the Fhl family, has also been implicated in the biological pathways of muscle growth and differentiation in PH 2-4 and is regulated by HIF-1a in a feedback loop that serves to limit HIF-1a activity under conditions of prolonged hypoxia. 5 MicroRNAs (miRs) are a class of B23-nucleotide, noncoding single-stranded RNAs that regulate gene function by identifying the 3 0 -untransl...

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Serum and Urinary Cell–free MiR-146a and MiR-155 in Patients with Systemic Lupus Erythematosus

Abstract: The results suggested that serum miR-146a and miR-155 participate in the pathophysiology of SLE and might be used as biomarkers of SLE.

Cited by 180 publications

References 28 publications

Cross‐regulation between cytokine and microRNA pathways in T cells

Cross‐regulation between cytokine and microRNA pathways in T cells

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

MicroRNA-206 is involved in hypoxia-induced pulmonary hypertension through targeting of the HIF-1α/Fhl-1 pathway

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