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Castrated autoimmune glomerulonephritis mouse model shows attenuated glomerular sclerosis with altered parietal epithelial cell phenotype

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Title: Castrated autoimmune glomerulonephritis mouse model shows attenuated glomerular sclerosis with altered parietal epithelial cell phenotype
Authors: Otani, Yuki Browse this author
Ichii, Osamu Browse this author →KAKEN DB
Masum, Md. Abdul Browse this author
Namba, Takashi Browse this author
Nakamura, Teppei Browse this author →KAKEN DB
Kon, Yasuhiro Browse this author →KAKEN DB
Keywords: Autoimmune disease
kidney disease
glomerular sclerosis
Issue Date: 1-Jun-2021
Publisher: SAGE Publications
Journal Title: Experimental biology and medicine
Volume: 246
Issue: 11
Start Page: 1318
End Page: 1329
Publisher DOI: 10.1177/1535370221996010
Abstract: Sex hormones help in maintaining proper immunity as well as renal homeostasis in mammals, and these multi-functional properties characterize the onset of sex-dependent diseases. To clarify the contribution of sex hormones to autoimmune disease-related renal pathogenesis, BXSB/MpJ-Yaa was investigated as a murine autoimmune glomerulonephritis model. BXSB/MpJ-Yaa and its wild-type, BXSB/MpJ-Yaa(+) were castrated or sham-operated at three weeks and examined until six months of age. Both castrated strains showed significantly lower serum testosterone levels and body weights than sham-operated mice. Castration did not change the disease phenotypes in BXSB/MpJ-Yaa(+). At three months, both sham-operated and castrated BXSB/MpJ-Yaa manifested splenomegaly, autoantibody production, and glomerulonephritis, and castrated BXSB/MpJ-Yaa tended to show heavier spleen weights than the sham-operated group. At six months, both the treated BXSB/MpJ-Yaa showed equivalent autoimmune disease conditions; however, castrated mice clearly showed milder glomerular sclerotic lesions than the sham-operated groups. Urinary albumin excretion in castrated BXSB/MpJ-Yaa was significantly milder than in sham-operated mice at four months, but those of both the treated BXSB/MpJ-Yaa were comparable at six months. The examined renal histopathological indices in parietal epithelial cells were remarkably altered by castration. Briefly, castration decreased the height of parietal epithelial cells and total parietal epithelial cell number in BXSB/MpJ-Yaa at six months. For immunostaining, parietal epithelial cells facing the injured glomeruli of BXSB/MpJ-Yaa expressed CD44, an activated parietal epithelial cell marker, and CD44-positive parietal epithelial cells showed nuclear localization of the androgen receptor and proliferation marker Ki67. CD44- or Ki67-positive parietal epithelial cells were significantly fewer in castrated group than in sham-operated BXSB/MpJ-Yaa at six months. Further, quantitative indices for CD44-positive parietal epithelial cell number and frequency in renal corpuscles positively correlated with glomerular sclerotic severity in BXSB/MpJ-Yaa. In conclusion, androgen seemed to have an effect on both systemic immunity and renal morpho-function; however, the effect on the latter could be more clearly observed in BXSB/MpJ-Yaa, as parietal epithelial cell activation resulted in glomerular sclerosis.
Rights: Otani Y, Ichii O, Masum MA, Namba T, Nakamura T, Kon Y. Castrated autoimmune glomerulonephritis mouse model shows attenuated glomerular sclerosis with altered parietal epithelial cell phenotype. Experimental Biology and Medicine. 2021;246(11):1318-1329. doi:10.1177/1535370221996010
Type: article (author version)
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 昆 泰寛

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