• Yonghong Yang, Kazuhide Ohta, Masaki Shimizu, Kayoko Morimoto, Chinami Goto, Akiko Nakai, Tomoko Toma, Yoshihito Kasahara, Akihiro Yachie, Hidetoshi Seki, and Shoichi Koizumi.
• Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
• Kidney Int. 2003 Oct 1; 64 (4): 1302-9.

BackgroundThe renal pathology of human heme oxygenase (HO)-1 deficiency is characterized by advanced tubulointerstitial injury, whereas the glomerular structures are affected little. These facts suggest that the renal tubuli are dependent on intrinsic HO-1 production for their survival under oxidative stresses.MethodsWe compared the patterns of HO-1 expression by primary cultured human mesangial cells (HMCs) and renal proximal tubular epithelial cells (HRPTECs) in vitro. Furthermore, the cytoprotective roles of HO-1 induced in these cells were evaluated by stress-induced cytotoxicity assays. HO-1 expressions in HRPTECs and HMCs were evaluated by immunoblotting, and by reverse transcriptase (RT) and/or real time polymerase chain reaction (PCR).ResultsIn HRPTECs, both HO-1 mRNA expression and protein production peaked at around 12 h and persisted until 24 h after hemin stimulation. In contrast, HO-1 mRNA expression and protein production by HMCs peaked at 4 h and 6 h respectively, and the levels declined rapidly, being undetectable at 24 h. The peak level of HO-1 expression was significantly higher in HRPTECs than in HMCs. Oxidative stress-induced cell injury in HRPTECs was significantly reduced when HO-1 production had been induced prior to the culture. In contrast, HO-1 induction had little cytoprotective effect on HMCs. Tin protoporphyrin (SnPP), an inhibitor of HO function, significantly reversed the cytoprotection by HO-1.ConclusionThese data suggest that HRPTECs are more susceptible to oxidative stress and are significantly more dependent on HO-1 for protection against noxious stimuli than HMCs. Collectively, these results indicate that HO-1 is an important protective factor for kidney tissue, in particular, renal tubular epithelial cells.

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