Changes to signal peptide and the level of transforming growth factor- 尾1 due to T869C polymorphism of TGF 尾1 associated with lupus renal fibrosis

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• 作者：Hani Susianti ; Kusworini Handono ; Basuki B Purnomo ; Nashi Widodo…
• 关键词：T869C gene polymorphism of TGF尾1 ; Signal peptide ; Urinary TGF尾1 level ; Renal fibrosis ; Lupus nephritis
• 刊名：SpringerPlus
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：3
• 期：1
• 全文大小：446KB
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• 作者单位：Hani Susianti (1)
  Kusworini Handono (1)
  Basuki B Purnomo (2)
  Nashi Widodo (3)
  Atma Gunawan (4)
  Handono Kalim (4)
  
  1. Department of Clinical Pathology, Faculty of Medicine Brawijaya University/Dr. Saiful Anwar Hospital, Malang, Indonesia
  2. Department of Urology, Faculty of Medicine Brawijaya University/Dr. Saiful Anwar Hospital, Malang, Indonesia
  3. Department of Biology, Faculty of Science, Brawijaya University, Malang, Indonesia
  4. Department of Internal Medicine, Faculty of Medicine Brawijaya University/Dr. Saiful Anwar Hospital, Malang, Indonesia
  
• 刊物类别：Science, general;
• 刊物主题：Science, general;
• 出版者：Springer International Publishing
• ISSN：2193-1801

文摘

Lupus Nephritis (LN) is a serious manifestation of lupus that can lead to End Stage Renal Disease (ESRD). Fibrosis is the main feature of ESRD, and it is likely influenced by Transforming Growth Factor Beta1 (TGF尾1). The T869C gene polymorphism of TGF尾1 is assumed to change the signal peptide, that has potential to interfere the urine production and renal protein expression of TGF尾1. The influence of T869C gene polymorphism on TGF尾1 production and renal fibrosis was evaluated in this study. Subjects were 45 patients LN with renal fibrosis and 45 participants without renal fibrosis as control, that were recruited from 2011 to 2013.Their urinary TGF尾1 levels and TGF尾1 gene polymorphisms were examined. All lupus patients underwent renal biopsy to assess their protein expression of TGF尾1 in the renal tissue by immunohistochemistry and their renal fibrosis by morphometry and chronicity index. Changes in the signal peptide interaction with Signal Recognition Particle (SRP) and translocon of endoplasmic reticulum were analyzed by Bioinformatics. Levels of urinary and protein expression of TGF尾1 increased in the LN with renal fibrosis group. There were significant differences in levels of urinary TGF尾1 in T, C allele and TT, TC, CC genotypes between case and control groups. Furthermore, patients with C allele are 3.86 times more at risk of renal fibrosis than T allele. The C allele encodes proline, which stabilizes the interaction of the TGF尾1 signal peptide with SRP and translocon, resulting in elevation of TGF尾1 secretion. Our results indicated that T869C gene polymorphism of TGF尾1 changes the signal peptide, that contributes to the production of urinary TGF尾1 and affects renal fibrosis in lupus nephritis. Keywords T869C gene polymorphism of TGF尾1 Signal peptide Urinary TGF尾1 level Renal fibrosis Lupus nephritis