Qi R.,Guangzhou University |
Li W.,HaiNan Provincial Hospital of Skin Disease |
Yu S.,Guangzhou University
Renal Failure | Year: 2014
TGF-β1 plays an important role in the pathogenesis of chronic renal diseases. Although the specific mechanism is unknown, a major factor is the potent fibrogenic activity of TGF-β1 in the chronic progression of renal diseases. TGF-β1 closely correlates with renal fibrosis in cooperation with several fibrosis-promoting molecules. Recently it has been studied that, Smad proteins as intracellular mediators of TGF-β signaling pathways provide important insights into the mechanisms determining the specificity of TGF-β action in various renal cells. Some studies have proved that immunosuppressants can affect TGF-β expression, but the mechanisms are unclear. In this study, we investigated the effect of FK506 on mesangial cells via TGF-β and Smads signal pathways. Our results shows that FK506 effectively blocked the TGF-β/Smad signaling pathway by downregulation of TGF-β receptor, and played an important role in TGF-β1-induced Smad2 expression in mice mesangial cells. FK506 can inhibit the TGF-β1-stimulated cell proliferation via Smad-related pathways. And reduced the Smad2 protein and mRNA expression. Altogether, this study provided a theoretical proof for the protective and treating effect of FK506 on kidneys. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.
Liu Q.,Hainan Provincial Hospital of Skin Disease |
Wu W.,Hainan Provincial Hospital of Skin Disease |
Lu J.,Hainan Provincial Hospital of Skin Disease |
Wang P.,Hainan Provincial Hospital of Skin Disease |
Qiao F.,Hainan Provincial Hospital of Skin Disease
Molecular Medicine Reports | Year: 2015
Steatocystoma multiplex (SM) is an uncommon disorder, characterized by numerous skin-colored subcutaneous cysts. A number of SM pedigrees have been identified with mutations in the keratin 17 (KRT17) gene. The present study examined a four-generation Chinese pedigree with an autosomal dominant mode of inheritance and examined its genetic basis. A review of the literature on KRT17 gene mutations in the SM pedigree was also performed to investigate the KRT17 gene mutation and genotype-phenotype correlation. Exon 1 of the KRTl7 gene was amplified using polymerase chain reaction (PCR) from genomic DNA obtained, which was obtained from 25 family members in the selected Chinese pedigree and from 100 unrelated control individuals. The DNA was then subjected to automatic DNA sequencing. Genealogical investigations demonstrated an autosomal dominant pattern, and direct sequencing of the PCR product revealed a heterozygous mutation, c.280C/T (R94C), which was located in exon 1 of the KRT17 gene in all 10 affected family members. The mutation was not identified in the 15 unaffected family members or in the 100 unrelated control individuals. Therefore, the present study identified a causative mutation in the KRT17 gene in a large Chinese SM pedigree, exhibiting autosomal dominance. A review of the literature suggested that, in addition to the mutation factor, other modifying factors contribute to the phenotype of familial SM.