Increased synthesis of extracellular matrix in mesangial proliferative nephritis.
Extracellular matrix expansion is frequently noted in mesangioproliferative renal diseases. This study investigates the role of immunologic factors in glomerular matrix accumulation. The gene expression of type I and IV collagen, laminin and s-laminin was examined in the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Northern analysis was performed on glomerular RNA isolated one, three and five days after disease induction and at day 3 following prior complement depletion. Tissue was immunostained for the protein products of these genes as well as for heparan sulfate proteoglycan, entactin and PCNA (a marker of cell proliferation) at days 1, 3, 5, 14, 21 and 42. A seven- to ten-fold increase of collagen IV and laminin mRNA as well as de novo expression of collagen I mRNA occurred at days 3 and 5 corresponding to the time of maximal proliferation. S-laminin mRNA levels only increased three-fold. With the exception of s-laminin, mesangial staining for all examined matrix proteins increased to a maximum at day 5 and decreased thereafter. Focal alterations of the glomerular architecture and matrix persisted at day 42. Complement depletion prevented the histological abnormalities as well as the increased expression of matrix proteins at day 3. These findings indicate that immunologic injury in the mesangium may result in overproduction of extracellular matrix components and may ultimately contribute to the development of glomerulosclerosis.
Department of Medicine, University of Washington, Seattle.
J
J
Floege
R J
RJ
Johnson
K
K
Gordon
H
H
Iida
P
P
Pritzl
A
A
Yoshimura
C
C
Campbell
C E
CE
Alpers
W G
WG
Couser
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D000961:Antilymphocyte Serum / Q000276:immunology; D003165:Complement System Proteins / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000096:biosynthesis*; D007116:Immunization, Passive; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D011509:Proteoglycans / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D000961:Antilymphocyte Serum; D003165:Complement System Proteins; D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; D012333:RNA, Messenger; D018800:Thy-1 Antigens