当前位置： SCI文献检索 > JOURNAL OF CELLULAR BIOCHEMISTRY期刊下所有文献 > Albumin induces cellular fibrosis by upregulating transforming growth factor-beta ligand and its receptors in renal distal tubule cells.

Albumin induces cellular fibrosis by upregulating transforming growth factor-beta ligand and its receptors in renal distal tubule cells.

Abstract：

:Albuminuria is indicative of nephropathy. However, little literature has focused on the role of albumin in renal distal tubule fibrosis. We used a well-defined distal tubule cell, Madin-Darby Canine Kidney (MDCK). Proliferation and cytotoxicity were examined. The conditioned supernatant was collected and subjected to ELISA assay for detection of fibronectin and TGF-beta1. Reverse transcription-PCR and Western blot assay were performed to evaluate the expression of mRNA and protein of two types of TGF-beta receptors (TbetaR). Flow cytometry assay and phosphotyrosine (pY)-specific antibodies were used to assay the phosphorylation status of TbetaR. We showed that albumin dose dependently (0, 0.1, 1, or 10 mg/ml) inhibited cellular growth in MDCK cells without inducing cellular cytotoxicity. In addition, albumin significantly upregulated the secretion of both fibronectin and TGF-beta1 at dose over 1 mg/ml. Moreover, 24 h pretreatment of albumin significantly enhanced exogenous TGF-beta1-induced secretion of fibronectin. These observations were reminiscent of the implications of TbetaR since TbetaR appears to correlate with the susceptibility of cellular fibrosis. We found that albumin significantly increased protein levels of type I TbetaR (TbetaRI) instead of type II receptors (TbetaRII). In addition, phosphorylation level of TbetaRII of both pY259 and pY424 was significantly enhanced instead of pY336. The novel observation indicates that extreme dose of albumin upregulates TGF-beta autocrine loop by upregulating TGF-beta1, TbetaRI, and the receptor kinase activity of TbetaRII by inducing tyrosine phosphorylation on key amino residue of TbetaRII in renal distal tubule cells. These combinational effects might contribute to the pathogenesis of renal fibrosis.

journal_name

J Cell Biochem

journal_title

Journal of cellular biochemistry

authors

Liu HC,Liao TN,Lee TC,Chuang LY,Guh JY,Liu SF,Hu MS,Yang YL,Lin SH,Hung MY,Huang JS,Hung TJ,Chen CD,Chiang TA,Chan JY,Chen SY,Yang YL

doi

10.1002/jcb.20673

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

956-68

issue

eissn

0730-2312

issn

1097-4644

journal_volume

pub_type

杂志文章

在线工具

Albumin induces cellular fibrosis by upregulating transforming growth factor-beta ligand and its receptors in renal distal tubule cells.