Enhanced expression of naofen in kidney of streptozotocin-induced diabetic rats: possible correlation to apoptosis of tubular epithelial cells (original) (raw)

Abstract

Background

Hyperglycemia/high glucose may induce apoptosis in diabetic kidney, but the mechanism is not fully understood. Naofen was found as a Shiga toxin (Stx)-2-related protein. Based on renal dysfunction in infection with Stx-producing Escherichia coli and on participation of naofen in apoptosis of human embryonic kidney cells, the present study was undertaken to investigate the mechanism of renal dysfunction in diabetes mellitus with particular reference to naofen.

Methods

In in vivo studies utilizing streptozotocin (STZ)-induced diabetic rats, and also in in vitro cultured rat kidney epithelial (NRK52E) cells, naofen messenger RNA (mRNA) and protein expressions were analyzed. Naofen mRNA location in diabetic kidney was studied by in situ hybridization. Apoptosis was assessed by caspase-3 activity assay.

Results

Rat diabetic kidney showed significant increases in caspase-3 activities and naofen mRNA. Naofen was mainly observed at both proximal and distal urinary tubules. Incubation of NRK52E cells in high glucose medium resulted in elevated naofen mRNA expression, whereas neither interleukin-1, interleukin-6, nor tumor necrosis factor-α elicited such action. Moreover, treatment of NRK52E cells with naofen small interfering RNA (siRNA) inhibited naofen mRNA expression induced by high glucose and blocked the increase in caspase-3 activity.

Conclusions

These data suggest that naofen expression may be upregulated by hyperglycemia, with possible correlation to apoptosis of tubular epithelial cells and thereby to diabetic nephropathy.

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Authors and Affiliations

  1. Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi-gun, Aichi, 480-1195, Japan
    Yuko Sato, Shuji Kurokawa, Yoshihiro Fujiwara & Toru Komatsu
  2. Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi-gun, Aichi, 480-1195, Japan
    Guo-Gang Feng, Lei Huang, Koji Tsunekawa, Fumio Kondo & Naohisa Ishikawa
  3. Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
    Jun-Hua Fan
  4. Heping District Center for Disease Control and Prevention, 76 Heping Street, Heping District, Shenyang, 110005, People’s Republic of China
    Chang Li
  5. Division of Gastroenterological Surgery, Department of Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi-gun, Aichi, 480-1195, Japan
    Jun An

Authors

  1. Yuko Sato
  2. Guo-Gang Feng
  3. Lei Huang
  4. Jun-Hua Fan
  5. Chang Li
  6. Jun An
  7. Koji Tsunekawa
  8. Shuji Kurokawa
  9. Yoshihiro Fujiwara
  10. Toru Komatsu
  11. Fumio Kondo
  12. Naohisa Ishikawa

Corresponding author

Correspondence toLei Huang.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s10157-010-0287-y

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Sato, Y., Feng, GG., Huang, L. et al. Enhanced expression of naofen in kidney of streptozotocin-induced diabetic rats: possible correlation to apoptosis of tubular epithelial cells.Clin Exp Nephrol 14, 205–212 (2010). https://doi.org/10.1007/s10157-010-0276-1

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