Increased class A scavenger receptor and glomerular lipid precede mesangial matrix expansion in the bGH mouse model.
OBJECTIVE
Elevated neutral lipid content and mRNA expression of class A scavenger receptor (SRA) have been found in the renal cortex of the bovine growth hormone (bGH) mouse model of progressive glomerulosclerosis (GS). We hypothesize that the increased expression of SRA precedes glomerular scarring in this model.


METHODS
Real time RT-PCR and immunofluorescence were employed to measure SRA and collagen types I and IV in the bGH transgenic and control mice at 5 and 12 weeks (wk) of age to determine the chronology of change in SRA expression in relation to glomerular scarring. Alternative mechanisms for increasing glomerular lipid were assessed by measuring mRNA expression levels of low-density lipoprotein receptor (LDL-r), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), and ATP-binding cassette transporter A1 (ABCA1). In addition, the involvement of macrophages in early GS was assessed by CD68 mRNA expression in kidney cortex.


RESULTS
Both mRNA and protein levels of SRA were significantly increased in 5-wk bGH compared with control mice, whereas the expression of collagen I and IV was unaltered. Unchanged levels of LDL-r and HMGR mRNA indicate that neither regulated cholesterol uptake via LDL-r nor the cholesterol synthetic pathway played a role in the early lipid increase. The finding of increased ABCA1 expression was an indicator of excess intracellular lipid in the renal cortex of bGH mice at 5 wk. CD68 expression in bGH did not differ significantly from that of controls at 5 wk suggesting that cortical macrophage infiltration was not increased in bGH mice at this time point.


CONCLUSIONS
An early increase in SRA mRNA and protein expression in the bGH kidney precedes glomerular scarring and is independent of macrophage influx.
Doi
Sonia Q
SQ
Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. sdoi@usuhs.mil
Chilakamarri
Geetha C
GC
Mendonca
Maria C
MC
Araujo
Magali
M
Nguyen
Nga
N
Zuhl
Irina
I
List
Edward O
EO
Kopchick
John J
JJ
Hirata
Mario H
MH
Sellitti
Donald F
DF
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005920:Glomerular Mesangium / Q000737:chemistry; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008055:Lipids; D012333:RNA, Messenger; D011973:Receptors, LDL; D051117:Scavenger Receptors, Class A; C073294:growth hormone, bovine; D013006:Growth Hormone