Platelet-derived growth factor (PDGF) and PDGF receptor are induced in mesangial proliferative nephritis in the rat.
We investigated whether platelet-derived growth factor (PDGF), or its receptor (PDGF-R), was upregulated in a rat model of mesangial proliferative glomerulonephritis. A marked increase in both PDGF A- and B-chain mRNA could be demonstrated in glomerular RNA by Northern blot analysis 3 and 5 days after disease induction, corresponding to the time of mesangial cell proliferation. PDGF-R beta-subunit mRNA and protein were also increased in glomeruli in mesangial proliferative nephritis, being maximal at day 5. The principal cells expressing PDGF B-chain appeared by immunostaining to be a subpopulation of mesangial cells; in contrast, the majority of the mesangial cells expressed the PDGF-R beta-subunit protein. Both complement depletion and platelet depletion significantly reduced cell proliferation and expression of both PDGF and PDGF-R. Thus, in mesangial proliferative nephritis there is a platelet- and complement-mediated induction of PDGF A and B chain and PDGF-R beta-subunit gene transcription and protein synthesis. The finding that the majority of PDGF is produced by the mesangial cell supports the role of PDGF as an autocrine growth factor in glomerulonephritis.
Iida
H
H
Department of Medicine, University of Washington, Seattle 98195.
Seifert
R
R
Alpers
C E
CE
Gronwald
R G
RG
Phillips
P E
PE
Pritzl
P
P
Gordon
K
K
Gown
A M
AM
Ross
R
R
Bowen-Pope
D F
DF
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D003165:Complement System Proteins / Q000502:physiology; D005920:Glomerular Mesangium / Q000473:pathology* / Q000503:physiopathology; D005921:Glomerulonephritis / Q000235:genetics* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology / Q000502:physiology; D046911:Macromolecular Substances; D008264:Macrophages / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000235:genetics*; D017479:Receptors, Platelet-Derived Growth Factor
D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012313:RNA; D003165:Complement System Proteins; D017479:Receptors, Platelet-Derived Growth Factor