Cloning of a novel gene in the human kidney homologous to rat munc13s: its potential role in diabetic nephropathy.
Glomerular mesangial cells (MC) are believed to play a pivotal role in development of diabetic nephropathy. We employed differential display reverse transcription polymerase chain reaction (DDRT-PCR) comparing human MC grown under 25 mM and 5.5 mM D-glucose and osmolarity control as a first step to identify possible candidate genes regulated by hyperglycemia. This strategy resulted in cloning of a novel gene in human MC, human munc13 (hmunc13), a human homologue of rat munc13s with the N-terminal segment similar to munc13-1 and the C-terminal segment more similar to munc13-2. Hmunc13 is also expressed in human kidney cortical epithelial cells. By using relative RT-PCR and Northern blot, we have confirmed that expression of hmunc13 in MC is up-regulated by high D-glucose treatment. Together with previous reports that munc13s binds to diacylglycerol (DAG) and that hyperglycemia increases DAG levels, these findings point to a potential role of hmunc13 in mediating some of the acute and chronic changes in MC produced by exposure to hyperglycemia.
Song
Y
Y
MRC Membrane Biology Group, Department of Medicine, University of Toronto, Ontario, Canada.
Ailenberg
M
M
Silverman
M
M
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular / Q000379:methods*; D003928:Diabetic Nephropathies / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000502:physiology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009994:Osmolar Concentration; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C485548:UNC13B protein, human; C103912:Unc13a protein, rat; D005947:Glucose