title: Pro-inflammatory/Th1 gene expression shift in high glucose stimulated mesangial cells and tubular epithelial cells.
abstract: 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/Th1 phenotype in mesangial cells and TECs, which might initiate and/or prolong inflammation, thereby resulting in diabetic nephropathy.
authors.affiliation: Division of Infection Control, Kanazawa University, Japan; Division of Nephrology, Kanazawa University, Japan. Electronic address: iwata-knz@umin.ac.jp.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Division of Nephrology, Kanazawa University, Japan; Division of Blood Purification, Kanazawa University, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Furuichi
authors.affiliation: Department of Laboratory Medicine, Kanazawa University, Japan; Department of Molecular Preventive Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Laboratory Medicine, Kanazawa University, Japan.
authors.forename: Kiyonobu
authors.initials: K
authors.lastname: Yokota
authors.affiliation: Department of Laboratory Medicine, Kanazawa University, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Yasuda
authors.affiliation: Division of Nephrology, Kanazawa University, Japan; Division of Blood Purification, Kanazawa University, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Sakai
authors.affiliation: Division of Nephrology, Kanazawa University, Japan; Department of Disease Control and Homeostasis, Kanazawa University, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kitajima
authors.affiliation: Division of Nephrology, Kanazawa University, Japan; Department of Disease Control and Homeostasis, Kanazawa University, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Toyama
authors.affiliation: Division of Nephrology, Kanazawa University, Japan; Department of Laboratory Medicine, Kanazawa University, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shinozaki
authors.affiliation: Division of Nephrology, Kanazawa University, Japan; Department of Disease Control and Homeostasis, Kanazawa University, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sagara
authors.affiliation: Department of Molecular Preventive Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Division of Nephrology, Kanazawa University, Japan; Department of Laboratory Medicine, Kanazawa University, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
mesh_terms: D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology*; D050527:Mesangial Cells / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018925:Chemokines; D058847:Inflammasomes; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D058570:TOR Serine-Threonine Kinases; D005947:Glucose
keywords: Diabetic nephropathy; Genome-wide analysis; Inflammation; Mesangial cells; Tubular epithelial cells