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Effect and mechanism of hyperhomocysteinemia induced podocyte injury in Henoch Schonlein purpura nephritis CBS+/- mice |
CHEN Leigang1, YANG Xiaojing1, FENG Dongmei1, WU Yuanhui1, WANG Shining1, GUO Baozhu2 |
1. Department of Dermatology, 2. Department of Nephrology, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China |
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Abstract Objective To study the effect and mechanism of homocysteinemia (HHcy) - induced podocyte injury in Henoch Schonlein purpura nephritis (HSPN) cystathionine -β- synthase (CBS) heterozygous mutation (CBS+/-) mice. Methods HSPN model was established in wild type CBS (CBS+/+) mice and CBS+/-mice, then given conventional diet or high methionine diet respectively. The levels of serum Hcy, renal pathological and ultrastructural changes, serum creatinine (Scr), blood urea nitrogen (BUN), 24-hour urinary protein, the expression of podocin, nephrin and podocalyxin were compared. Results The renal pathological changes were found in the CBS+/++HSPN group and the high methionine diet CBS+/++HSPN group, and the levels of Scr, BUN and 24h urinary protein were higher than those in the conventional diet CBS+/+ group, but there was no significant difference in the renal pathological changes, Scr, BUN and 24h urinary protein levels between the high methionine diet CBS+/++HSPN group and the conventional diet CBS+/++ HSPN group. Renal pathological and ultrastructural changes were observed in conventional diet CBS+/-+HSPN group, Scr, BUN and 24h urinary protein levels were higher than those of conventional diet CBS+/- group, the expression of podocin, nephrin and podocalyxin were lower than those of conventional diet CBS+/- group; compared with conventional diet CBS+/-+HSPN group, renal athological and ultrastructural changes aggravated, Hcy, Scr, BUN and 24h urinary protein levels increased, the expression of podocin, nephrin and podocalyxin decreased of high methionine diet CBS+/- group; compared with high methionine diet CBS+/- group, renal athological and ultrastructural changes improved, Hcy, Scr, BUN and 24h urinary protein levels decreased, the expression of podocin, nephrin and podocalyxin increased in folic acid+ high methionine diet CBS+/- group. Conclusion HHcy can promote renal pathological changes and podocyte injury in HSPN CBS+/- mice, and inhibit the expression of transmembrane proteins podocin, nephrin and podocalyxin is a possible molecular mechanism.
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Received: 22 July 2022
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