Dataset Information

Peroxisome proliferator-activated receptor-? agonist troglitazone suppresses transforming growth factor-?1 signalling through miR-92b upregulation-inhibited Axl expression in human keloid fibroblasts in vitro.

ABSTRACT: Keloid, a skin benign tumor, is characterized by overgrowth of fibroblasts and the excessive deposition of extracellular matrix in wounded skin. Peroxisome proliferator-activated receptor-? (PPAR-?) agonist was recently evaluated to inhibit fibrosis. This study explored the underlying mechanisms. Fibroblasts isolated from 25 keloid patients (KFs) and fibroblasts isolated from healthy controls (NSFBs) were also subjected to treatment with PPAR-? agonist troglitazone and antagonist GW9662 or for transfection with miR-92 mimics or inhibitor, Axl siRNA, and miR-92b or Axl promoter constructs, as well as being subjected to qRT-PCR, ELISA, Western blot, protein array, luciferase, and ChIP assays. The data demonstrated that TGF-?1 and Axl proteins were significantly elevated in samples from keloid patients, while troglitazone treatment significantly reduced levels of TGF-?1 and Axl mRNA and proteins in KFs. Moreover, knockdown of Axl expression reduced expression of TGF-?1 and its pathway genes (such as ?-SMA and Snail). PPAR-? regulation of Axl expression was through transcriptional activation of miR-92b. miR-92b expression downregulated Axl expression at both mRNA and protein levels, whereas GW9662 completely reversed the inhibitory effects of miR-92b mimics on Axl expression. Gene ontology analysis of miR-92b targeting genes showed that TGF-? and Axl were both potential targets of miR-92b, as confirmed by luciferase assay. These findings demonstrated that PPAR-?-induced miR-92b expression inhibited Axl expression and in turn reduced expression of TGF-?1 and the downstream genes in KFs, suggesting that targeting of this novel gene pathway may be useful for therapeutic control of fibrosis or keloid.

SUBMITTER: Zhu HY

PROVIDER: S-EPMC5009398 | biostudies-other | 2016

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Peroxisome proliferator-activated receptor-γ agonist troglitazone suppresses transforming growth factor-β1 signalling through miR-92b upregulation-inhibited Axl expression in human keloid fibroblasts in vitro.

Zhu Hua-Yu HY Bai Wen-Dong WD Li Jun J Tao Ke K Wang Hong-Tao HT Yang Xue-Kang XK Liu Jia-Qi JQ Wang Yun-Chuan YC He Ting T Xie Song-Tao ST Hu Da-Hai DH

American journal of translational research 20160815 8

Keloid, a skin benign tumor, is characterized by overgrowth of fibroblasts and the excessive deposition of extracellular matrix in wounded skin. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist was recently evaluated to inhibit fibrosis. This study explored the underlying mechanisms. Fibroblasts isolated from 25 keloid patients (KFs) and fibroblasts isolated from healthy controls (NSFBs) were also subjected to treatment with PPAR-γ agonist troglitazone and antagonist GW9662 or for t ...[more]

PMID: 27648136

Similar Datasets

Project description:Rheumatoid arthritis (RA), a chronic inflammatory disease, is associated with insulin resistance. Experimental evidence indicates that the relationship between insulin resistance and inflammation is bidirectional: Inflammation promotes insulin resistance, and insulin resistance promotes inflammation. Therefore, we examined the hypothesis that pioglitazone, a thiazolidinedione peroxisome proliferator-activated receptor ? agonist, would decrease inflammation and disease activity and improve insulin resistance in patients with RA.In a single-center, randomized, double-blind, placebo-controlled crossover study patients with RA (N = 34) receiving stable therapy were randomized to also receive either pioglitazone 45 mg daily (n = 17) or matching placebo (n = 17) for eight weeks. This was followed by a four-week washout period and alternative treatment for eight weeks. Outcomes included change in Disease Activity Score in 28 joints (DAS28) score, individual components of the DAS28 score and homeostatic model assessment for insulin resistance (HOMA). Intention-to-treat analysis and linear mixed-effects models were used.Patients had a mean (± SD) age of 51 (± 14.2) years, 82.4% were female and baseline DAS28 high-sensitivity C-reactive protein (DAS28-CRP) was 4.58 (± 1.1) units. Addition of pioglitazone was associated with a 9.3% reduction (95% confidence interval (CI) = 0.17% to 17.6%) in DAS28-CRP (P = 0.046), but no significant change in DAS28 erythrocyte sedimentation rate (DAS28-ESR) (P = 0.92). There was a 10.7 mm (95% CI = 0.4 to 20.9 mm) improvement in patient-reported global health (P = 0.042), a 48.6% decrease (95% CI = 27.6% to 63.5%) in CRP (P < 0.001) and a 26.4% decrease (95% CI = 3.7% to 43.8%) in insulin resistance as measured by HOMA (P = 0.025), but no significant reduction in swollen or tender joint count or in ESR (all P > 0.05). Lower-extremity edema was more common during pioglitazone treatment (16%) than placebo (0%).Addition of pioglitazone to RA therapy improves insulin resistance and modestly reduces RA disease activity measured by DAS28-CRP and two of its components, including patient-reported global health and CRP, but not DAS28-ESR or ESR.NCT00763139.

Dataset Information

Peroxisome proliferator-activated receptor-? agonist troglitazone suppresses transforming growth factor-?1 signalling through miR-92b upregulation-inhibited Axl expression in human keloid fibroblasts in vitro.

Publications

Peroxisome proliferator-activated receptor-γ agonist troglitazone suppresses transforming growth factor-β1 signalling through miR-92b upregulation-inhibited Axl expression in human keloid fibroblasts in vitro.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets