Pro-inflammatory/Th1 gene expression shift in high glucose stimulated mesangial cells and tubular epithelial cells

被引：14

作者：

Iwata, Yasunori ^{[1
,2
]}

Furuichi, Kengo ^{[2
,3
]}

Hashimoto, Shinichi ^{[4
,6
]}

Yokota, Kiyonobu ^{[4
]}

Yasuda, Haruka ^{[4
]}

Sakai, Norihiko ^{[2
,3
]}

Kitajima, Shinji ^{[2
,5
]}

Toyama, Tadashi ^{[2
,5
]}

Shinozaki, Yasuyuki ^{[2
,4
]}

Sagara, Akihiro ^{[2
,5
]}

Matsushima, Kouji ^{[6
]}

Kaneko, Shuichi ^{[5
]}

Wada, Takashi ^{[2
,4
]}

机构：

[1] Kanazawa Univ, Div Infect Control, Kanazawa, Ishikawa 9208641, Japan

[2] Kanazawa Univ, Div Nephrol, Kanazawa, Ishikawa 9208641, Japan

[3] Kanazawa Univ, Div Blood Purificat, Kanazawa, Ishikawa 9208641, Japan

[4] Kanazawa Univ, Dept Lab Med, Kanazawa, Ishikawa 9208641, Japan

[5] Kanazawa Univ, Dept Dis Control & Homeostasis, Kanazawa, Ishikawa 9208641, Japan

[6] Univ Tokyo, Dept Mol Prevent Med, Tokyo, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2014年 / 443卷 / 03期

关键词：

Diabetic nephropathy; Inflammation; Genome-wide analysis; Mesangial cells; Tubular epithelial cells; ACTIVATED PROTEIN-KINASE; ACUTE KIDNEY INJURY; DIABETIC-NEPHROPATHY; T-CELLS; NLRP3; INFLAMMASOME; MRL-FAS(LPR) MICE; PATHOGENIC ROLE; RENAL INJURY; P38; POLARIZATION;

D O I：

10.1016/j.bbrc.2013.12.072

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：

Diabetic nephropathy (DN) is a major cause of end stage kidney disease and a strong risk factor for cardiovascular diseases. Growing data show chronic inflammation plays an important role for the progression of DN. As for the immune cells, anti-inflammatory leukocytes as well as pro-inflammatory leukocytes play an important role in DN. In addition to leukocytes, renal resident cells contribute to the inflammatory process of DN. However, precise functions, phenotypes and immune balance of renal resident cells remain to be explored. Therefore, we hypothesized that the aberrant immune balance of renal resident cells contributes to the pathogenesis of DN. To explore this possibility, we performed genome-wide transcriptome profiling in mesangial cells and tubular epithelial cells (TECs), which were stimulated by high glucose (HG) and detected the expression of inflammation associated genes. HG increased the mRNA expression of oxidative stress, inflammasome and mammalian target of rapamycin (mTOR) related genes in mesangial cells. Pro-inflammatory/Th1 gene expression was upregulated, but Th2 related gene expression was downregulated in mesangial cells. In TECs, HG stimulation increased pro-inflammatory/Th1/Th2 gene expression. Phosphorylation of signaling proteins shifted towards pro-inflammatory phenotype with suppressed phosphorylation of Th2 related signaling in TECs. The data taken together indicate that HG shifts the immune balance toward pro-inflammatory/Thl phenotype in mesangial cells and TECs, which might initiate and/or prolong inflammation, thereby resulting in diabetic nephropathy. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：969 / 974

页数：6

共 39 条

[11] p38 mitogen-activated protein kinase contributes to autoimmune renal injury in MRL-Faslpr mice [J].