NDT Advance Access published online on April 12, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl120
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1 Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Hirokoji, Kawaramachi-dori, Kamikyo-ku, Kyoto, 602-8566, Japan
* To whom correspondence should be addressed. Background. Integrin-linked kinase (ILK) is a protein that plays an important role in extracellular matrix-mediated signalling. Recent studies implicated ILK dysregulation in the development of diabetic nephropathy. However, little is known about the significance of ILK up-regulation in response to high glucose in mesangial cells. Methods. The ILK messenger (m)RNA and protein expression in human mesangial cells were analysed with quantitative real-time polymerase chain reaction (PCR) and western blotting after exposure to either 100, 200, or 500 mg/dl glucose, or 100 mg/dl glucose + 400 mg/dl mannitol. Activation of protein Kinase B (PKB)/Akt was also determined by western blot analysis. Cells were transfected with ILK siRNA to determine the effects of ILK knockdown on PKB/Akt activation and cell death following treatment with high glucose or mannitol. Results. High concentrations of glucose or mannitol for three days significantly up-regulated ILK mRNA and protein expression (P<0.05 vs 100 mg/dl glucose). In contrast, ILK expression in cells exposed to the same conditions for seven days was unaffected. The time course of PKB/Akt phosphorylation was similar to that of ILK protein expression. The siRNA-mediated down-regulation of ILK expression inhibited the elevation of PKB/Akt phosphorylation induced by high glucose treatment. Furthermore, the inhibition of ILK expression promoted high glucose- or mannitol-induced apoptosis. Conclusion. The ILK may act as a pro-survival factor and play a role in protecting mesangial cells from hyperglycaemic osmotic stress.
Received January 28, 2006
Accepted February 24, 2006
Original Article
Integrin-linked kinase acts as a pro-survival factor against high glucose-associated osmotic stress in human mesangial cells
Masayoshi Ohnishi 1,
Goji Hasegawa 1 *,
Masahiro Yamasaki 1,
Hiroshi Obayashi 2,
Michiaki Fukui 1,
Toshiki Nakajima 1,
Yukiko Ichida 1,
Hiroyuki Ohse 1,
Shin-ichi Mogami 1,
Toshikazu Yoshikawa 3,
and
Naoto Nakamura 1
2 Institute of Bio-Response Informatics, Kyoto, Japan
3 Department of Inflammation and Immunology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Hirokoji, Kawaramachi-dori, Kamikyo-ku, Kyoto, 602-8566, Japan
Goji Hasegawa, E-mail: goji{at}koto.kpu-m.ac.jp
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