title: Possible roles of tumor necrosis factor-α and angiotensin II type 1 receptor on high glucose-induced damage in renal proximal tubular cells.
abstract: Recent studies have identified that high glucose-induced renal tubular cell damage. We previously demonstrated that high glucose treatment induced oxidative stress in human renal proximal tubular epithelial cells (RPTECs), and angiotensin II type 1 (AT1) receptor blockers reduce high glucose-induced oxidative stress in RPTEC possibly via blockade of intracellular as well as extracellular AT1 receptor. However, exact roles of tumor necrosis factor (TNF)-α and AT1 receptor on high glucose-induced renal tubular function remain unclear. N-acetyl-beta-glucosaminidase (NAG), concentrations of TNF-α/angiotensin II and p22(phox) protein levels after high glucose treatment with or without AT1 receptor blocker or thalidomide, an inhibitor of TNF-α protein synthesis, were measured in immortalized human renal proximal tubular epithelial cells (HK2 cells). AT1 receptor knockdown was performed with AT1 receptor small interfering RNA (siRNA). High glucose treatment (30 mM) significantly increased NAG release, TNF-α/angiotensin II concentrations in cell media and p22(phox) protein levels compared with those in regular glucose medium (5.6 mM). Candesartan, an AT1R blocker, showed a significant reduction on high glucose-induced NAG release, TNF-α concentrations and p22(phox) protein levels in HK2 cells. In addition, significant decreases of NAG release, TNF-α concentrations and p22(phox) protein levels in HK2 cells were observed in high glucose-treated group with thalidomide. AT1R knockdown with siRNA markedly reversed high glucose, angiotensin II or TNF-α-induced p22(phox) protein levels in HK2 cells. TNF-α may be involved in high glucose-induced renal tubular damage in HK2 cells possibly via AT1 receptor signaling.
authors.affiliation: Department of Health Care Medicine, Kawasaki Medical School , Kurashiki , Japan and.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takao
authors.forename: Taro
authors.initials: T
authors.lastname: Horino
authors.forename: Reiko
authors.initials: R
authors.lastname: Matsumoto
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Shimamura
authors.forename: Koji
authors.initials: K
authors.lastname: Ogata
authors.forename: Kousuke
authors.initials: K
authors.lastname: Inoue
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Taguchi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Terada
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D000118:Acetylglucosaminidase; D005947:Glucose
keywords: Angiotensin II type 1 (AT1) receptor; HK2 cells; N-acetyl-beta-glucosaminidase; p22phox; tumor necrosis factor alpha