title: The Potential effect of G915C polymorphism in regulating TGF-β1 transport into Endoplasmic Reticulum for cytokine production.
abstract: 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.
authors.affiliation: Departement of Clinical Pathology, Faculty of Medicine, Brawijaya University, Malang, Indonesia.
authors.forename: Hani
authors.initials: H
authors.lastname: Susianti
authors.affiliation: Departement of Internal Medicine, Faculty of Medicine, Brawijaya University, Malang, Indonesia.
authors.forename: Atma
authors.initials: A
authors.lastname: Gunawan
authors.affiliation: Departement of Biology, Faculty of Sciences, Brawijaya University, Malang, Indonesia.
authors.forename: Jayarani Fatimah
authors.initials: JF
authors.lastname: Putri
authors.affiliation: Department of Urology, Faculty of Medicine, Brawijaya University, Malang, Indonesia.
authors.forename: Basuki B
authors.initials: BB
authors.lastname: Purnomo
authors.affiliation: Departement of Clinical Pathology, Faculty of Medicine, Brawijaya University, Malang, Indonesia.
authors.forename: Kusworini
authors.initials: K
authors.lastname: Handono
authors.affiliation: Departement of Internal Medicine, Faculty of Medicine, Brawijaya University, Malang, Indonesia.
authors.forename: Handono
authors.initials: H
authors.lastname: Kalim