Identification of a novel kidney-specific gene downregulated in acute ischemic renal failure

To gain further insights into the molecular mechanisms involved in acute re nal failure, we have isolated a new gene from rat and human, named KSP32 (k idney-specific protein with a molecular mass of 32 kDa). KSP32 encodes a no vel gene that shows little homology to other mammalian proteins. It, howeve r, shares extensive homology with several proteins found in the nematode Ca enorhabditis elegans and plants. The expression of KSP32 mRNA is highly res tricted to kidney. In situ hybidization analysis revealed that the expressi on of KSP32 mRNA was prominent in the boundary of kidney cortex and outer m edulla, exhibiting a raylike formation extending from the medulla into the cortex. Finally, KSP32 mRNA was dramatically downregulated in rat following induction of acute ischemic renal failure. Rapid loss of KSP32 mRNA expres sion was observed beginning at similar to 5 h following renal injury and mR NA levels remained depressed for at least 96 h. Both KSP32 mRNA levels as w ell as renal function recovered 14 days after injury. Administration of an endothelin receptor antagonist (SB-209670), known to restore renal function , significantly increased KSP32 expression.