Bradykinin and high glucose promote renal tubular inflammation

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
Sydney C W TangKar Neng Lai

Abstract

The role of the kallikrein-kinin system in diabetic nephropathy remains controversial. High-glucose (HG) super-induced interleukin (IL)-6, CCL-2, transforming growth factor (TGF)-beta, vascular endothelial growth factor (VEGF) and B(2)K receptor (B(2)KR) mRNA in cultured proximal tubular epithelial cells (PTEC), whereas bradykinin (BK) upregulated IL-6, CCL-2 and TGF-beta mRNA. HG activated mitogen-activated protein kinase (MAPK) p42/p44 and protein kinase C (PKC) signals, whereas BK only activated MAPK. Tubular expression of these mediators and tissue kallikrein 1 (KLK1) was confirmed in human diabetic kidney biopsies. Inhibition of MAPK p42/p44 by PD98059 partially reduced HG and BK induction of IL-6, CCL-2 and TGF-beta, whereas inhibition of PKC by staurosporine partially reduced HG- but not BK-induced overexpression of these cytokines and that of VEGF. Staurosporine and PD98059 synergistically reduced the effect of HG on IL-6, CCL-2 and TGF-beta expression. The B(2)KR blocker, icatibant, downregulated BK- and HG-induced MAPK p42/p44 but not HG-induced PKC activation and partially reduced both HG- and BK-induced IL-6, CCL-2 and TGF-beta secretion. HG stimulated expression of KLK1 and low-molecular-weight kininogen (LMWK) and...Continue Reading

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Citations

Jun 27, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Sydney C W Tang, Kar Neng Lai
Oct 25, 2011·Journal of the American Society of Nephrology : JASN·Miao LinSydney C W Tang
Feb 21, 2013·Kidney International·Miao LinSydney C W Tang
Jan 13, 2015·Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation·Sydney C W TangKar Neng Lai
Sep 10, 2014·Clinical Science·Rui Xi LiSydney C W Tang
May 11, 2015·Journal of Diabetes and Its Complications·Jing-Yu WangBao-Cheng Chang
Sep 30, 2014·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Lu LuHai-Li Xin
Jul 1, 2014·International Immunopharmacology·Gabriel R EstrelaRonaldo C Araújo
May 4, 2011·Laboratory Investigation; a Journal of Technical Methods and Pathology·Sydney C W TangKar Neng Lai
Mar 29, 2014·Journal of the American Society of Nephrology : JASN·Emily BorstingRobyn Cunard
Apr 5, 2013·Acta Histochemica Et Cytochemica·Shunsuke TakataHiroyuki Ishikawa
Jan 17, 2020·Nature Reviews. Nephrology·Sydney C W Tang, Wai Han Yiu
May 11, 2012·American Journal of Physiology. Renal Physiology·Nelly BlaesJean-Pierre Girolami
Mar 22, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hanying DingFan Fan Hou
Jul 26, 2021·European Journal of Pharmacology·João FariaRosalinde Masereeuw
Feb 3, 2022·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wenying ZhangJun Zhang

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