Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation.
Mesangial cell proliferation is common in glomerulonephritis but it is unclear if proliferation is associated with any in vivo alteration in phenotype. We investigated whether mesangial of mesangial proliferative nephritis induced with antibody to the Thy-1 antigen present on mesangial cells. At day 3 glomeruli displayed de novo immunostaining for alpha-smooth muscle actin in a mesangial pattern, correlating with the onset of proliferation, and persisting until day 14. An increase in desmin and vimentin in mesangial regions was also noted. Immunoelectron microscopy confirmed that the actin-positive cells were mesangial cells, and double immunolabeling demonstrated that the smooth muscle actin-positive cells were actively proliferating. Northern analysis of isolated glomerular RNA confirmed an increase in alpha and beta/gamma actin mRNA at days 3 and 5. Complement depletion or platelet depletion prevented or reduced proliferation, respectively; these maneuvers also prevented smooth muscle actin and actin gene expression. Studies of five other experimental models of nephritis confirmed that smooth muscle actin expression is a marker for mesangial cell injury. Thus, mesangial cell proliferation in glomerulonephritis in the rat is associated with a distinct phenotypic change in which mesangial cell assume smooth muscle cell characteristics.
Johnson
R J
RJ
Department of Medicine, University of Washington Seattle 98195.
Iida
H
H
Alpers
C E
CE
Majesky
M W
MW
Schwartz
S M
SM
Pritzi
P
P
Gordon
K
K
Gown
A M
AM
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001483:Base Sequence; D001792:Blood Platelets / Q000502:physiology; D015152:Blotting, Northern; D002454:Cell Differentiation; D002455:Cell Division; D003165:Complement System Proteins / Q000502:physiology; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism; D005921:Glomerulonephritis / Q000473:pathology*; D007105:Immune Complex Diseases / Q000473:pathology*; D007124:Immunoenzyme Techniques; D007382:Intermediate Filaments / Q000378:metabolism; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018800:Thy-1 Antigens
D000199:Actins; D000954:Antigens, Surface; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D003165:Complement System Proteins