Susianti Hani, Gunawan Atma, Putri Jayarani Fatimah, Purnomo Basuki B, Handono Kusworini, Kalim Handono
Departement of Clinical Pathology, Faculty of Medicine, Brawijaya University, Malang, Indonesia.
Departement of Internal Medicine, Faculty of Medicine, Brawijaya University, Malang, Indonesia.
Bioinformation. 2014 Aug 30;10(8):487-90. doi: 10.6026/97320630010487. eCollection 2014.
The TGF-β1 cytokine concentration is known to be higher in nephritis with implied Lupus Nephritis severity. The production of TGF-β1 cytokine is associated with G915C polymorphism. Therefore, it is of interest to study G915C polymorphism. The G915C polymorphism changes codon 25 which encodes arginine into proline in the signal peptide of TGF-β1. The amino acid substitution affects signal peptide properties that may inhibit the transport of TGF-β1 into the endoplasmic reticulum and eventually decline the cytokine production. Hence, the effect of G915C polymorphism on the properties of the signal peptide, the ability of TGF-β1 transport into the endoplasmic reticulum and the concentrations of urinary TGF-β1 in Lupus Nephritis patients was studied. The arginine substitution into proline decreased the polarity of the signal peptide for TGF-β1. The increased hydrophobicity with increased binding energy of the signal peptide for TGF-β1 to Signal Recognition Particle (SRP) and translocon is shown. This implies decreased protein complex stability in potentially blocking the transport of TGF-β1 into the endoplasmic reticulum. This transport retention possibly hampers the synthesis and maturation of TGF-β1 leading to decreased cytokine production.
已知在隐匿性狼疮性肾炎的肾炎中，转化生长因子-β1（TGF-β1）细胞因子浓度较高。TGF-β1细胞因子的产生与G915C多态性有关。因此，研究G915C多态性具有重要意义。G915C多态性使TGF-β1信号肽中编码精氨酸的第25位密码子变为脯氨酸。氨基酸替换影响信号肽特性，这可能会抑制TGF-β1转运至内质网，并最终降低细胞因子的产生。因此，研究了G915C多态性对狼疮性肾炎患者信号肽特性、TGF-β1转运至内质网的能力以及尿TGF-β1浓度的影响。精氨酸替换为脯氨酸降低了TGF-β1信号肽的极性。结果显示，TGF-β1信号肽与信号识别颗粒（SRP）和易位子的结合能增加，疏水性增强。这意味着在潜在地阻断TGF-β1转运至内质网的过程中，蛋白质复合物稳定性降低。这种转运滞留可能会阻碍TGF-β1的合成和成熟，导致细胞因子产生减少。
