Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models

Kimura, Junpei; Ichii, Osamu; Otsuka, Saori; Sasaki, Hayato; Hashimoto, Yoshiharu; Kon, Yasuhiro

Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models

Kimura, Junpei; Ichii, Osamu; Otsuka, Saori et al.

American Journal Of Nephrology, 2013, 38(1), 27-38

Permalink : https://hdl.handle.net/2115/53122

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アクセス権	open access
URI	https://hdl.handle.net/2115/53122
タイトル	Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models
著者	Kimura, Junpei ; Ichii, Osamu ; Otsuka, Saori ; Sasaki, Hayato ; Hashimoto, Yoshiharu ; Kon, Yasuhiro
著者名 Kimura, Junpei
e-Rad_Researcher 60547769 著者名 Ichii, Osamu
e-Rad_Researcher 10566152 著者名 Otsuka, Saori
著者名 Sasaki, Hayato
e-Rad_Researcher 20091481 著者名 Hashimoto, Yoshiharu
e-Rad_Researcher 10178402 著者名 Kon, Yasuhiro
言語	英語
キーワード	Autoimmune disease
	B6.MRL-(D1Mit202-D1Mit403)
	BXSB/MpJ
	Membranous proliferative glomerulonephritis
	Podocyte
	Systemic lupus erythematosus
発行日	2013-07
出版者	Karger
収録物名	American Journal Of Nephrology
巻(号)	38(1)
ページ	27-38
抄録	Background: Membranous proliferative glomerulonephritis (MPGN) is a major primary cause of chronic kidney disease (CKD). Podocyte injury is crucial in the pathogenesis of glomerular disease with proteinuria, leading to CKD. To assess podocyte injuries in MPGN, the pathological features of spontaneous murine models were analyzed. Methods: The autoimmune-prone mice strains BXSB/MpJ-Yaa and B6.MRL-(D1Mit202-D1Mit403) were used as the MPGN models, and BXSB/MpJ-Yaa(+) and C57BL/6 were used as the respective controls. In addition to clinical parameters and glomerular histopathology, the protein and mRNA levels of podocyte functional markers were evaluated as indices for podocyte injuries. The relation between MPGN pathology and podocyte injuries was analyzed by statistical correlation. Results: Both models developed MPGN with albuminuria and elevated serum anti-double-strand DNA (dsDNA) antibody levels. BXSB/MpJ-Yaa and B6.MRL showed severe proliferative lesions with T and B cell infiltrations and membranous lesions with T cell infiltrations, respectively. Foot process effacement and microvillus-like structure formation were observed ultrastructurally in the podocytes of both MPGN models. Furthermore, both MPGN models showed a decrease in immune-positive areas of nephrin, podocin and synaptopodin in the glomerulus, and in the mRNA expression of Nphs1, Nphs2, Synpo, Actn4, Cd2ap, and Podxl in the isolated glomerulus. Significant negative correlations were detected between serum anti-dsDNA antibody levels and glomerular Nphs1 expression, and between urinary albumin-to-creatinine ratio and glomerular expression of Nphs1, Synpo, Actn4, Cd2ap, or Podxl. Conclusion: MPGN models clearly developed podocyte injuries characterized by the decreased expression of podocyte functional markers with altered morphology. These data emphasized the importance of regulation of podocyte injuries in MPGN. Copyright (c) 2013 S. Karger AG, Basel
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Copyright (c) 2013 S. Karger AG, Basel
PISSN	0250-8095
NCID	AA10424676
関連情報	PMID 23817053
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1159/000353093