Renal processing of albumin in diabetes and hypertension in rats: possible role of TGF-beta1.
OBJECTIVE
Recent studies show that albuminuria may be the result of changes in post-glomerular cellular uptake and processing of albumin. This study aims to determine whether this processing is disrupted in diabetes and/or hypertension.


METHODS
Diabetes (d) was induced using streptozotocin in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) and studied after 8, 16 and 24 weeks of disease. Intact albumin excretion was determined by radioimmunoassay. Total albumin was determined by [(14)C]albumin. Lysosomal activity was determined by dextran sulfate desulfation. Renal TGF-beta1 and transforming growth factor-beta1 inducible gene-h3 mRNA (betaig-h3) expression was determined by real time RT-PCR.


RESULTS
SHR-c rats exhibited an increase in intact albuminuria without significant change in total albumin excretion (intact plus albumin-derived peptides). For WKY-d rats, intact albuminuria developed initially, followed by an increase in total albumin excretion primarily in the form of albumin peptides (peptiduria). SHR-d rats exhibited both increases in peptiduria and intact albuminuria. There was no increase in glomerular permeability at 24 weeks for polydisperse [(3)H]Ficoll in all groups. Increased renal TGF-beta1 and betaig-h3 expression was correlated with a decrease in dextran sulfate desulfation and increased intact albuminuria independent of peptiduria.


CONCLUSIONS
Increased albumin excretion in hypertension and/or diabetes is manifested in different forms independent of glomerular permeability.
Russo
Leileata M
LM
Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
Osicka
Tanya M
TM
Brammar
Gail C
GC
Candido
Riccardo
R
Jerums
George
G
Comper
Wayne D
WD
D000418:Albumins / Q000378:metabolism; D000419:Albuminuria; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010539:Permeability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014168:Transferrin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D000099222:betaIG-H3 Protein
D000418:Albumins; D016326:Extracellular Matrix Proteins; D006442:Glycated Hemoglobin; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014168:Transferrin; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein