Role of microRNA-146a in regulation of fibrosis in orbital fibroblasts from patients with Graves’ orbitopathy

Jang, Sun Young; Park, Seong Jun; Chae, Min Kyung; Lee, Joon H; Lee, Mi Kyung; Yoon, Jin Sook

doi:10.1136/bjophthalmol-2017-310723

Cited by 42 publications

(50 citation statements)

References 34 publications

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“…The increase in HA production and collagen deposition has been indicated to increase the volume of orbital tissue in GO, thereby aggravating the symptoms of eyeball protrusion (26). The results of the current study are consistent with those of a previous study, which reported that miR-146a downregulated the expression of collagen I and was associated with TGF-β-mediated fibrosis (11). In addition, the effect of miR-146a on HA production was examined in the present study, and it was revealed that overexpression of miR-146a inhibited HA production, which suggests that upregulation of miR-146a may reduce GAG aggregation in patients with GO.…”

Section: Discussionsupporting

confidence: 92%

“…Owing to the potent hydrophilic nature of HA, its accumulation has been indicated to accelerate the expansion of orbital tissues (10). Collagen I is considered to be a marker of fibrosis (11). Fibrocytes, which express CD34 and C-X-C chemokine receptor type 4, have been reported to produce collagen I and infiltrate tissues in response to multiple chemokines, including C-X-C motif chemokine 12 (12), which may result in fibrosis in orbital tissues.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-146a downregulates the production of hyaluronic acid and collagen I in Graves' ophthalmopathy orbital fibroblasts

Liu

Chen

et al. 2020

Exp Ther Med

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The present study aimed to investigate the effect of microRNA (miR)-146a on the secretion of hyaluronic acid (HA) and collagen I in Graves' ophthalmopathy (GO) orbital fibroblasts, and identify potential novel targets for the clinical treatment of GO. Orbital fibroblasts were extracted from orbital connective tissue, and primary cells were identified via immunohistochemistry. The levels of HA and collagen I in orbital fibroblasts of non-GO controls and patients with GO were examined via reverse transcription-quantitative PCR (RT-qPCR). miR-146a was overexpressed or inhibited in primary orbital fibroblasts via lentiviral infection, and the levels of HA and collagen I following miR-146a overexpression or inhibition were detected via ELISA and RT-qPCR. The results indicated that the mRNA expression of HA and collagen I was higher in orbital fibroblasts from patients with GO compared with the non-GO cohort. Overexpression of miR-146a reduced, and inhibition of miR-146a increased the production of HA and collagen I in GO orbital fibroblasts. In conclusion, it was demonstrated that miR-146a downregulated the secretion of HA and collagen I in GO orbital fibroblasts in vitro, which may affect glycosaminoglycan aggregation and collagen deposition in GO.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

MicroRNA-146a downregulates the production of hyaluronic acid and collagen I in Graves' ophthalmopathy orbital fibroblasts

Liu

Chen

et al. 2020

Exp Ther Med

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“…It has been recently documented that miR-146a-5p participates in the biogenesis of fibrosis in a variety of tissues [36][37][38][39][40]. In the pathogenesis of nonalcoholic fibrosing steatohepatitis, it has been shown that miR-146a-5p was significantly down-regulated in activated hepatic stellate cells (HSCs) and overexpression of miR-146a-5p suppressed HSC activation, as well as extracellular matrix deposition [41].…”

Section: Discussionmentioning

confidence: 99%

Serum Exosomal miRNAs for Grading Hepatic Fibrosis Due to Schistosomiasis

Cai

Olveda

et al. 2020

IJMS

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Chronic infection with Schistosoma japonicum or Schistosoma mansoni results in hepatic fibrosis of the human host. The staging of fibrosis is crucial for prognosis and to determine the need for treatment of patients with schistosomiasis. This study aimed to determine whether there is a correlation between the levels of serum exosomal micro-ribonucleic acids (miRNAs) (exomiRs) and fibrosis progression in schistosomiasis. Reference gene (RG) validation was initially carried out for the analysis of serum exomiRs expression in staging liver fibrosis caused by schistosome infection. The expression levels of liver fibrosis-associated exomiRs in serum were determined in a murine schistosomiasis model and in a cohort of Filipino schistosomiasis japonica patients (n = 104) with different liver fibrosis grades. Of twelve RG candidates validated, miR-103a-3p and miR-425-5p were determined to be the most stable genes in the murine schistosomiasis model and subjects from the schistosomiasis-endemic area, respectively. The temporal expression profiles of nine fibrosis-associated serum exomiRs, as well as their correlations with the liver pathologies, were determined in C57BL/6 mice during S. japonicum infection. The serum levels of three exomiRs (miR-92a-3p, miR-146a-5p and miR-532-5p) were able to distinguish subjects with fibrosis grades I-III from those with no fibrosis, but only the serum level of exosomal miR-146a-5p showed potential for distinguishing patients with mild (grades 0–I) versus severe fibrosis (grades II–III). The current data imply that serum exomiRs can be a supplementary tool for grading liver fibrosis in hepatosplenic schistosomiasis with moderate accuracy.

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“…The regulatory roles of miR-146a-5p in various types of fibrosis have been recently documented [ 15 , 20 , 24 , 34 , 48 ]. During S. japonicum infection, it was shown that miR-146 is considerably up-regulated in liver macrophages, suppressing the IFN-γ-induced differentiation of macrophages to M1 cells through targeting STAT1 [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNAs as footprints for liver fibrosis grading in schistosomiasis

Cai

Olveda

et al. 2018

EBioMedicine

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BackgroundChronic infection with Schistosoma japonicum or S. mansoni results in hepatic fibrosis of the human host. Staging fibrosis is crucial for the prognosis and to determine the rapid need of treatment in patients with schistosomiasis.MethodsTo establish whether there is a correlation between circulating microRNA (miRNA) level and fibrosis progression in schistosomiasis, ten miRNAs were selected to assess their potential in grading schistosomiasis liver fibrosis. This was done firstly in two mouse strains (C57BL/6 and BALB/c) to determine the temporal expression profiles in serum over the course of S. japonicum infection, and then within a cohort of 163 schistosomiasis japonica patients with different grades of liver fibrosis.FindingFour miRNAs (miR-150-5p, let-7a-5p, let-7d-5p and miR-146a-5p) were able to distinguish patients with mild versus severe fibrosis. The level of serum miR-150-5p showed the most promising potential for grading hepatic fibrosis in schistosomiasis. The diagnostic performance of miR-150-5p in discriminating mild from severe fibrosis is comparable with that of the ELF test and serum HA level. In addition, the serum levels of the four miRNAs rebounded in infected C57BL/6 mice, after 6 months post treatment, following the regression of liver fibrosis, thereby providing further support for the utility of these miRNAs in grading schistosomal hepatic fibrosis.Interpretation.Circulating miRNAs can be a supplementary tool for assessing hepatic fibrosis in human schistosomiasis.Fund (NHMRC) of Australia (APP1102926, APP1037304 and APP1098244).

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Role of microRNA-146a in regulation of fibrosis in orbital fibroblasts from patients with Graves’ orbitopathy

Abstract: miR-146a plays a role as a negative regulator in the production of TGF-β-induced fibrotic markers. Thus, miR-146a may be involved in the regulation of fibrosis in orbital fibroblasts from patients with GO.

Cited by 42 publications

References 34 publications

MicroRNA-146a downregulates the production of hyaluronic acid and collagen I in Graves' ophthalmopathy orbital fibroblasts

MicroRNA-146a downregulates the production of hyaluronic acid and collagen I in Graves' ophthalmopathy orbital fibroblasts

Serum Exosomal miRNAs for Grading Hepatic Fibrosis Due to Schistosomiasis

Circulating miRNAs as footprints for liver fibrosis grading in schistosomiasis

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