The lupus-derived anti-double-stranded DNA IgG contributes to myofibroblast-like phenotype in mesangial cells.
Anti-double-stranded DNA (dsDNA) antibodies have been indicated to play a major role in the pathogenesis of lupus nephritis (LN), which is characterized by mesangial alterations, including phenotypic changes. To explore the effects of anti-dsDNA antibodies on the phenotype of mesangial cells (MCs), the anti-dsDNA IgG in sera and histological features of glomeruli were analyzed in the mice models of immune-complex glomerulonephritis. The MCs were cultured in vitro with the addition of anti-dsDNA or non-anti-dsDNA IgG. Compared to the anti-dsDNA-negative controls, the serum positive mice had increased extracellular matrix accumulation and higher alpha-smooth muscle actin expression in the mesangial region. The anti-dsDNA IgG enhanced the synthesis of transforming growth factor beta, alpha-smooth muscle actin, and fibronectin, and even induced the myofibroblast-like morphological features in cultured MCs. Our results indicated that anti-dsDNA antibodies contribute to the phenotypic changes in MCs, which suggests another mechanism of renal injuries in LN induced by anti-dsDNA antibodies.
Department of Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Yi
Y
Zhang
Jiabin
J
Yang
Shan
S
Jiang
Chunhong
C
Fang
Layuan
L
Xiong
Hong
H
Cheng
Yumin
Y
Xia
D000199:Actins / Q000235:genetics / Q000276:immunology; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology / Q000494:pharmacology*; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000235:genetics / Q000276:immunology; D005353:Fibronectins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000166:cytology; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
D000199:Actins; D000974:Antibodies, Antinuclear; D005353:Fibronectins; D007074:Immunoglobulin G; D016212:Transforming Growth Factor beta; C544013:alpha-smooth muscle actin, mouse