Roles of layilin in TNF-α-induced epithelial-mesenchymal transformation of renal tubular epithelial cells

被引：36

作者：

Adachi, Takayuki ^{[1
,2
]}

Arito, Mitsumi ^{[1
]}

Suematsu, Naoya ^{[1
]}

Kamijo-Ikemori, Atsuko ^{[3
]}

Omoteyama, Kazuki ^{[1
]}

Sato, Toshiyuki ^{[1
]}

Kurokawa, Manae S. ^{[4
]}

Okamoto, Kazuki ^{[1
]}

Kimura, Kenjiro ^{[5
]}

Shibagaki, Yugo ^{[2
]}

Kato, Tomohiro ^{[1
]}

机构：

[1] St Marianna Univ, Grad Sch Med, Clin Prote & Mol Med, Kawasaki, Kanagawa 2168511, Japan

[2] St Marianna Univ, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Kawasaki, Kanagawa 2168511, Japan

[3] St Marianna Univ, Sch Med, Dept Anat, Kawasaki, Kanagawa 2168511, Japan

[4] St Marianna Univ, Grad Sch Med, Dis Biomarker Anal & Mol Regulat, Kawasaki, Kanagawa 2168511, Japan

[5] Japan Community Hlth Care Org, Tokyo Takanawa Hosp, Tokyo, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 467卷 / 01期

基金：

日本学术振兴会;

关键词：

Epithelial-mesenchymal transformation; Renal tubular epithelium; Glomerulonephritis; Layilin; TNF-alpha; HYALURONAN RECEPTOR; IGA NEPHROPATHY; CARCINOMA-CELLS; TRANSITION; FIBROSIS; PROGRESSION; MECHANISM; NEPHRITIS; CYTOKINES; PROTEIN;

D O I：

10.1016/j.bbrc.2015.09.121

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Tumor necrosis factor (TNE)-alpha is suggested to induce epithelial-mesenchymal transformation (EMT) of renal tubular epithelial cells that possibly exacerbates renal interstitial fibrosis in glomerulonephritis (GN). We here investigated whether layilin (LAYN), a c-type lectin-homologous protein, was involved in the EMT process. Methods: Expression of LAYN was investigated in kidneys of mice administered with TNF-alpha and in a clear cell renal carcinoma cell line of KMRC-1 stimulated with TNF-alpha by quantitative polymerase chain reaction (qPCR) and/or western blotting. Expression of LAYN was assessed immunohistochemically in renal biopsy samples of patients with various types of GN. Changes of EMT markers and cell morphology by TNF-alpha and transforming growth factor (TGF)-beta in LAYN-knocked down KMRC-1 cells were investigated by qPCR and immunocytochemistry. Results: Administration of TNF-alpha increased expression of LAYN in renal tubular epithelia in mice. TNF-alpha but not TGF-beta increased expression of LAYN in KMRC-1 cells. Renal biopsy samples from the patients with GN showed high expression of LAYN in tubular epithelial cells. TNF-alpha induced up-regulation of vimentin, down-regulation of E-cadherin, and fibroblast-like morphological change in KMRC-1 cells, indicating occurrence of EMT. These changes were not observed in the LAYN-knocked down cells. In contrast, similarly occurred TGF-beta-induced EMT was not affected by the LAYN knockdown. Conclusion: Our data indicate that LAYN is involved in the TNF-alpha-induced EMT of renal tubular epithelial cells. LAYN may play roles in the generation of renal interstitial fibrosis in GN via TNF-alpha-induced EMT. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：63 / 69

页数：7

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