Identification of a novel kidney-specific gene downregulated in acute ischemic renal failure.
To gain further insights into the molecular mechanisms involved in acute renal failure, we have isolated a new gene from rat and human, named KSP32 (kidney-specific protein with a molecular mass of 32 kDa). KSP32 encodes a novel gene that shows little homology to other mammalian proteins. It, however, shares extensive homology with several proteins found in the nematode Caenorhabditis elegans and plants. The expression of KSP32 mRNA is highly restricted to kidney. In situ hybidization analysis revealed that the expression of KSP32 mRNA was prominent in the boundary of kidney cortex and outer medulla, 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 expression was observed beginning at approximately 5 h following renal injury and mRNA levels remained depressed for at least 96 h. Both KSP32 mRNA levels as well 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.
Hu
E
E
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19403, USA. Erding_Hu-1@sbphrd.com
Chen
Z
Z
Fredrickson
T
T
Gellai
M
M
Jugus
M
M
Contino
L
L
Spurr
N
N
Sims
M
M
Halsey
W
W
Van Horn
S
S
Mao
J
J
Sathe
G
G
Brooks
D
D
D058186:Acute Kidney Injury / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D015536:Down-Regulation / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D050562:Inositol Oxygenase; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D007679:Kidney Medulla / Q000737:chemistry / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000098:blood supply / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D010088:Oxidoreductases; D010105:Oxygenases; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid
D011506:Proteins; D012333:RNA, Messenger; D010088:Oxidoreductases; D010105:Oxygenases; D050562:Inositol Oxygenase; C485890:MIOX protein, human; C414007:Miox protein, rat