Moreover, the role of cytokine (interleukin-1β, interleukin-6) and connective tissue growth factor (CTGF) production, and extracellular signal-regulated kinases (ERK) activation in mediating P2X7R-dependent pro-fibrotic effects in SSc fibroblasts was evaluated.
Since IRF5, STAT4, and IRAK1 are important regulatory factors in the control of innate immune responses and CTGF is involved in the synthesis of extracellular matrix, these results suggest a role of the innate immunity and matrix compounds in the pathogenesis of PF in SSc.
We demonstrated that Repsox has the most potent inhibitory effects on TGF-β-induced expression of CTGF and collagen of cultured normal dermal fibroblasts in vitro and their constitutive overexpression of scleroderma fibroblast in vitro.
Expression levels of other TGF-β-regulated genes, including SERPINE1 and CTGF, declined (P = 0.049 and P = 0.012, respectively), and a 2-gene, longitudinal pharmacodynamic biomarker of SSc skin disease decreased after fresolimumab treatment (P = 0.0067).
Polymorphisms in exons 2-4 for HLA-A, -B, -C loci, exon 2 for HLA-DRB1 and exons 2,3 for HLA-DQB1 were analyzed for association with PSS at allele and haplotype levels.
Importantly, the inhibitory and stimulatory effects of rapamycin on the mRNA levels of COL1A2 and MMP1 genes, respectively, were significantly greater in SSc dermal fibroblasts than in normal dermal fibroblasts.
Targeting the myofibroblast genetic switch: inhibitors of myocardin-related transcription factor/serum response factor-regulated gene transcription prevent fibrosis in a murine model of skin injury.
Targeting the myofibroblast genetic switch: inhibitors of myocardin-related transcription factor/serum response factor-regulated gene transcription prevent fibrosis in a murine model of skin injury.
A novel small-molecule inhibitor of MRTF/SRF-regulated transcription (CCG-203971) inhibits expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen 1 (COL1A2) in both SSc fibroblasts and in lysophosphatidic acid (LPA)-and transforming growth factor β (TGFβ)-stimulated fibroblasts.
Our results suggest that γ/δ T cells showed activated phenotype in SSc and suggest that SSc γ/δ T cells may play an important role on fibrotic process by upregulation of COL1A2 mRNA expression in fibroblasts.
Connective tissue growth factor (CTGF) has been implicated in the cardiac and kidney complications of type 2 diabetes, and the CTGF-945 G/C polymorphism is associated with susceptibility to systemic sclerosis, a disease characterised by tissue fibrosis.
Our investigations revealed that roscovitine coordinately inhibited the expression of collagen, fibronectin, and connective tissue growth factor (CTGF) in normal and SSc fibroblasts.
Connective tissue growth factor (CCN2) gene expression was significantly reduced and matrix metalloproteinase 1 (MMP1) levels were enhanced after ciprofloxacin treatment to a similar extent in healthy and SSc fibroblasts.
Three orthologues of genes implicated in human SSc are located in the QTL region on chromosome 2, TGFRB1, EXOC2-IRF4 and COL1A2, as well as CCR8, which is more generally related to immune function.
In conclusion, this study has revealed an important role of cav-1 in mediating TGFβ/Smad1 signaling and CCN2 gene expression in healthy and SSc dermal fibroblasts.
Moreover, IL-17A, not IL-17F, reduced the protein expression of α1(I) collagen and connective tissue growth factor. miR-129-5p, one of the downregulated microRNAs in SSc fibroblasts, increased due to IL-17A and mediated the α1(I) collagen reduction.
Although many studies have analyzed HLA allele frequencies in several ethnic groups in patients with scleroderma (SSc), none has been done in French Caucasian patients and none has evaluated which one of the common amino acid sequences, (67)FLEDR(71), shared by HLA-DRB susceptibility alleles, or (71)TRAELDT(77), shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to develop the disease.
Induction of matrix metalloproteinase-1 by small interfering RNA targeting connective tissue growth factor in dermal fibroblasts from patients with systemic sclerosis.
We assessed the possible association between 7 single-nucleotide polymorphisms (SNP) in the CTGF gene and scleroderma in a French population (registration number 2006/0182).