title: Podocyte-specific deletion of signal transducer and activator of transcription 3 attenuates nephrotoxic serum-induced glomerulonephritis.
abstract: Activation of signal transducer and activator of transcription (STAT)3 correlates with proliferation of extracapillary glomerular epithelial cells and the extent of renal injury in glomerulonephritis. To delineate the role of STAT3 in glomerular epithelial cell proliferation, we examined the development of nephrotoxic serum-induced glomerulonephritis in mice with and without podocyte-restricted STAT3 deletion. Mice with STAT3 deletion in podocytes developed less crescents and loss of renal function compared with those without STAT3 deletion. Proliferation of glomerular cells, loss of podocyte markers, and recruitment of parietal epithelial cells were found in nephritic mice without STAT3 deletion, but mitigated in nephritic mice with podocyte STAT3 deletion. Glomerular expression of pro-inflammatory STAT3 target genes was significantly reduced in nephritic mice with, compared with those without, podocyte STAT3 deletion. However, the extent of glomerular immune complex deposition was not different. Podocytes with STAT3 deletion were resistant to interleukin-6-induced STAT3 phosphorylation and pro-inflammatory STAT3 target gene expression. Thus, podocyte STAT3 activation is critical for the development of crescentic glomerulonephritis.
authors.affiliation: 1] Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA [2] Division of Nephrology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dai
authors.forename: Leyi
authors.initials: L
authors.lastname: Gu
authors.forename: Weijie
authors.initials: W
authors.lastname: Yuan
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Ni
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ross
authors.forename: Lewis
authors.initials: L
authors.lastname: Kaufman
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
authors.forename: David J
authors.initials: DJ
authors.lastname: Salant
authors.forename: John C
authors.initials: JC
authors.lastname: He
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Chuang
mesh_terms: D000419:Albuminuria / Q000378:metabolism; D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D003176:Complement C3 / Q000378:metabolism; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000378:metabolism; D005921:Glomerulonephritis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007136:Immunoglobulins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture; D050796:STAT3 Transcription Factor / Q000172:deficiency* / Q000235:genetics; D044967:Serum; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D000936:Antigen-Antibody Complex; D003176:Complement C3; D007136:Immunoglobulins; D018836:Inflammation Mediators; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D004815:Epidermal Growth Factor