Anti-liver fibrosis activities of the extracellular domain of transforming growth factor beta type II receptor fusion protein in vivo / 中国药科大学学报

@#This study is performed to analyze the anti-liver fibrosis effect of the fusion protein of human serum albumin and extracellular domain of transforming growth factor beta type II receptor(eTGFBR2)in vivo to looking for the more stable anti-liver fibrosis drug. The mice model of liver fibrosis was constructed by CCl4 induction and the following groups are included in the study: the control group, CCl4 model group, the positive control group, eTGFBR2 treatment group, HSA-eTGFBR2 treatment group, and HSA group. Hematoxylin eosin staining, serum liver function index detection, and western blot are used to identify the anti-liver fibrosis activities. The results showed that: (1)CCl4 caused liver structure disorder, hepatocellular necrosis, collagen fibers proliferation, and induced liver fibrosis at last; (2)HSA-eTGFBR2 and its monomer drug improved the symptoms of liver fibrosis significantly, as well as reduced the damage of liver cells and collagen deposition, and recovered the liver basic structure to normal. Both of HSA-eTGFBR2 and its monomer drug improved liver function and reduced the expression level of liver fibrosis marker α-SMA and COL I. Moreover, the anti-liver fibrosis effect of the fusion protein is comparable to the monomer drug. In contrast, the albumin had no effect on therapeutic effect; (3)Reducing the injection frequency of HSA-eTGFBR2 achieved the comparable effects to the monomer drug with the normal injection frequency. In summary, the fusion protein HSA-eTGFBR2 has good anti-liver fibrosis effect. In addition, reducing the injection frequency of the fusion protein could also achieve the comparable treatment with the monomer drug, indicating that the fusion protein is stable and has longer half-lives and then a relatively positive application prospect in future.

Síndrome de Loeys-Dietz, una mutación en el gen TGFBR2, primer reporte en el suroccidente colombiano / Loeys-Dietz syndrome, a mutation in TGFBR2 gene, first report in the colombian suroccident

Resumen: el síndrome de Loeys-Dietz es una rara enfermedad genética, autosómica dominante, con hábito marfanoide, que pertenece a un subconjunto de enfermedades del tejido conectivo con afectación esquelética, ocular y cardiovascular, principalmente. El desarrollo de aneurismas es característico en esta patología. El síndrome de Loeys-Dietz es causado por mutaciones en los genes TGFBR1, TGFBR2, TGFB2, TGFB3 Y SMAD3. En este manuscrito se describe el caso clínico de un paciente masculino, de 22 meses de vida, con una dilatación importante de la raíz aórtica y arco aórtico elongado cuya prueba molecular confirma el diagnóstico de síndrome de Loeys-Dietz, asociado a una mutación en el gen TGFBR2. Este corresponde al primer caso reportado en el suroccidente colombiano. (AU)

Abstract: Loeys-Dietz syndrome is a rare, autosomal dominant genetic disease, with marfanoid habit, which belongs to a subset of diseases of the connective tissue with mainly skeletal, ocular, and cardiovascular involvement. Aneurysms development is characteristic in this pathology. Loeys-Dietz syndrome is caused by mutations in TGFBR1, TGFBR2, TGFB2, TGFB3 and SMAD3 genes. In this manuscript is presented the clinical case of a 22-month-old male patient with significant dilatation of the aortic root and elongated aortic arch is described. The molecular test confirms the diagnosis of Loeys-Dietz syndrome associated with a mutation in the TGFBR2 gene. This corresponds to the first case reported in the southwestern Colombian. (AU)

A Case of Near Total Aortic Replacement in an Adolescent With Loeys-Dietz Syndrome

Loeys-Dietz syndrome is a recently described autosomal dominant disorder caused by mutations in the genes for transforming growth factor-beta receptor type 1 or 2 (TGF-ssR 1/2). The syndrome predisposes patients to aortic aneurysm and dissections, along with craniofacial and musculoskeletal abnormalities. Here we report the case of an adolescent who underwent serial near total aortic replacement, from the aortic valve to the descending aorta. Loeys-Dietz syndrome was confirmed in this case by the detection of a mutation in the TGF-ssR 2 gene.

Transforming growth factor beta receptor II polymorphisms are associated with Kawasaki disease / 소아과

PURPOSE: Transforming growth factor beta receptor 2 (TGFBR2) is a tumor suppressor gene that plays a role in the differentiation of striated cells and remodeling of coronary arteries. Single nucleotide polymorphisms (SNPs) of this gene are associated with Marfan syndrome and sudden death in patients with coronary artery disease. Cardiovascular remodeling and T cell activation of TGFBR2 gene suggest that the TGFBR2 gene SNPs are related to the pathogenesis of Kawasaki disease (KD) and coronary artery lesion (CAL). METHODS: The subjects were 105 patients with KD and 500 healthy adults as controls. Mean age of KD group was 32 months age and 26.6% of those had CAL. We selected TGFBR2 gene SNPs from serum and performed direct sequencing. RESULTS: The sequences of the eleven SNPs in the TGFBR2 gene were compared between the KD group and controls. Three SNPs (rs1495592, rs6550004, rs795430) were associated with development of KD (P=0.019, P=0.026, P=0.016, respectively). One SNP (rs1495592) was associated with CAL in KD group (P=0.022). CONCLUSION: Eleven SNPs in TGFBR2 gene were identified at that time the genome wide association. But, with the change of the data base, only six SNPs remained associated with the TGFBR2 gene. One of the six SNPs (rs6550004) was associated with development of KD. One SNP associated with CAL (rs1495592) was disassociated from the TGFBR2 gene. The other five SNPs were not functionally identified, but these SNPs are notable because the data base is changing. Further studies involving larger group of patients with KD are needed.