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Dissecting the role of transforming growth factor-?1 in topmouth culter immunobiological activity: a fundamental functional analysis.

ABSTRACT: Transforming growth factor-?1 (TGF-?1) has been proven to function primarily in mammalian immunobiological activity, but information regarding the immune role of TGF-?1 in teleosts is limited. In the present study, we describe the cDNA cloning and characterization of the TGF-?1 molecule in the topmouth culter. TGF-?1 is highly expressed in immune-related tissues of the culter, including the thymus, head kidney, and spleen. The recombinant culter TGF-?1 (cTGF-?1) was successfully expressed and purified in vitro, and the effects of cTGF-?1 on the mRNA expression of pro-inflammatory cytokines, such as TNF-? and IL-1?, in the absence or presence of LPS was determined in culter peripheral blood leukocytes. cTGF-?1 was found to have bipolar properties in inflammatory reactions. Additionally, to assess the immune role of teleost TGF-?1 in vivo, the expression of TGF-?1 in the culter thymus and spleen tissues induced by poly I:C were also examined. The expression of TGF-?1 was obviously up-regulated, as shown in the cell lines. However, the peak time of cTGF-?1 expression in the cell lines occurred significantly earlier than in the organic tissues under the same inducer, suggesting that the response of the teleost TGF-?1 molecule to exogenous infection depends on a more complicated signalling pathway in vivo than in vitro.

SUBMITTER: Qi P

PROVIDER: S-EPMC4890032 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Dissecting the role of transforming growth factor-β1 in topmouth culter immunobiological activity: a fundamental functional analysis.

Qi Pengzhi P Xie Congxin C Guo Baoying B Wu Changwen C

Scientific reports 20160602

Transforming growth factor-β1 (TGF-β1) has been proven to function primarily in mammalian immunobiological activity, but information regarding the immune role of TGF-β1 in teleosts is limited. In the present study, we describe the cDNA cloning and characterization of the TGF-β1 molecule in the topmouth culter. TGF-β1 is highly expressed in immune-related tissues of the culter, including the thymus, head kidney, and spleen. The recombinant culter TGF-β1 (cTGF-β1) was successfully expressed and pu ...[more]

PMID: 27251472

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Project description:Fabry disease is a lysosomal storage disorder (LSD) caused by deficiency of α-galactosidase A (α-gal A), resulting in deposition of globotriaosylceramide (Gb3; also known as ceramide trihexoside) in the vascular endothelium of many organs. A gradual accumulation of Gb3 leads to cardiovascular, cerebrovascular and renal dysfunction. Endothelial cell dysfunction leads to renal complications, one of the main symptoms of Fabry disease. However, the pathological mechanisms by which endothelial dysfunction occurs in Fabry disease are poorly characterized. The purpose of this study was to investigate whether the expression of transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) is associated with the renal pathogenesis of Fabry disease. We found that the protein expression levels of renal thrombospondin-1 (TSP-1), TGF-β1 and VEGF were higher in the kidneys from Fabry mice compared to wild-type mice. The expression levels of VEGF receptor 2 (VEGFR2), fibroblast growth factor-2 (FGF-2) and phospho-p38 (P-p38) were also higher in the kidneys from Fabry mice compared with wild-type mice. Activities of cysteine aspartic acid protease (caspase)-6 and caspase-9 were higher in kidneys from Fabry than from the wild-type mice. These results suggest that overexpression of TGF-β1 and VEGF in the Fabry mouse kidney might contribute to Fabry disease nephropathy by inducing apoptosis. To test whether Gb3 accumulation can induce apoptosis, we incubated bovine aortic endothelial cells with Gb3 and found increased expression of TGF-β1, VEGFR2, VEGF, FGF-2 and P-p38. The combination of increased expression of TGF-β1 and VEGF caused by Gb3 accumulation may allow upregulation of FGF-2, VEGFR2 and P-p38 expression, and these changes may be associated with Fabry disease nephropathy by inducing apoptosis.

Dataset Information

Dissecting the role of transforming growth factor-?1 in topmouth culter immunobiological activity: a fundamental functional analysis.

Publications

Dissecting the role of transforming growth factor-β1 in topmouth culter immunobiological activity: a fundamental functional analysis.

Similar Datasets

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