Addition of oleic acid to delipidated bovine serum albumin aggravates renal damage in experimental protein-overload nephrosis.
BACKGROUND
Non-esterified fatty acids (NEFA) carried on albumin may have a causal role in the development of chronic proteinuria-induced nephropathy. To investigate whether NEFA aggravate renal structural damage, we studied the effects of NEFA addition to delipidated bovine serum albumin (BSA) in protein-overload nephropathy.


METHODS
Three groups of Wistar rats received daily intraperitoneal injections (3 weeks) of either 1 g NEFA-free BSA (BSA-0), or NEFA-free BSA with three (BSA-3) or six (BSA-6) molecules oleic acid added per BSA molecule. An additional group received saline injections only (SAL). Renal damage was evaluated by immunohistochemistry and RT-PCR.


RESULTS
Interstitial and glomerular alpha-smooth muscle actin (alpha-SMA, marker of myofibroblast transformation) expression were higher in BSA-3/6 than in saline-injected controls (P < 0.001). Glomerular macrophage influx and desmin (marker of glomerular epithelial cell damage) expression were higher in all BSA-injected rats than SAL (P < 0.001). Interstitial macrophage influx was elevated in BSA-0/3 (P < 0.05) and BSA-6 (P < 0.001) compared to SAL. Addition of six molecules of oleic acid to BSA revealed higher interstitial and glomerular alpha-SMA expression (P < 0.001), increased interstitial macrophage numbers (P < 0.001) and enhanced glomerular desmin expression (P < 0.05) compared to BSA-0. RT-PCR revealed higher glomerular alpha-SMA mRNA expression in BSA-3/6 than SAL (P < 0.001 and 0.05, respectively), interstitial alpha-SMA mRNA was elevated in BSA-6 (P < 0.05). Interstitial TGF-beta1 mRNA expression was significantly higher in BSA-3 than SAL (P < 0.05).


CONCLUSIONS
These data show that addition of oleic acid to NEFA-free BSA aggravates renal damage, suggesting a role for NEFA in the pathogenesis of proteinuric nephropathies.
van Timmeren
Mirjan M
MM
Department of Pathology and Laboratory Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. m.m.van.timmeren@path.umcg.nl
Bakker
Stephan J L
SJ
Stegeman
Coen A
CA
Gans
Rijk O B
RO
van Goor
Harry
H
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D009401:Nephrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D019301:Oleic Acid / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D019301:Oleic Acid; D012333:RNA, Messenger; D012710:Serum Albumin, Bovine; D016212:Transforming Growth Factor beta; C498862:Acta2 protein, rat