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Abstract: FR-PO730

Study on the Pathogenesis of the Leu754Val Mutation of the ARHGAP32 Gene Inducing Focal Segmental Glomerulosclerosis

Session Information

Category: Glomerular Diseases

  • 1304 Glomerular Diseases: Podocyte Biology


  • Chen, Pei Si, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
  • Li, Guisen, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China

Focal segmental glomerulosclerosis (FSGS) is one of the most common causes of refractory nephrotic syndrome and end-stage renal disease. Previous studies indicated that genetic factors play an important role in the pathogenesis of FSGS. A new candidate pathogenic gene, ARHGAP32 gene (c.1213C>G, p.Leu405Val), was found in FSGS family, which may be the cause of FSGS. This project is based on the previous studies, through in vitro and in vivo studies, to preliminarily explore the mechanism of ARHGAP32 expression changes and mutations leading to podocyte damage, and to provide new ideas for the pathogenesis of FSGS and new treatment measures.


The function of ARHGAP32 gene mutation was studied by in vivo and in vitro experiments, and the protein expression level was studied. After the construction of Arhgap32 gene mutation mice, adriamycin was injected into tail vein to establish the kidney injury model of Arhgap32 mutant mice. Urine, blood and kidney tissue samples were collected to detect the related biochemical indexes and pathological analysis; the markers of podocyte, nephrin and synaptopodin, were detected to study the effect of ARHGAP32 gene mutation on podocytes and the mechanism of podocyte injury induced by ARHGAP32 gene mutation.


Immunohistochemical staining showed that there were protein expressions in the kidney of Arhgap32 mutant mice. After adriamycin induced Arhgap32 gene mutation mice, weight gain slowed down, proteinuria appeared, serum creatinine and urea nitrogen levels increased, renal tissue showed glomerular mesangial cell proliferation and other renal pathological damage, the podocyte markers Nephrin and Synaptopodin expression decreased, podocyte injury occurred. The expression of Rac1, RhoA and CDC42, which may be affected by Rho GTPase family members, was detected, and the expression of Rac1, RhoA and CDC42 in the mutant mice was increased.


This study showed that ARHGAP32 gene was highly expressed in renal tissue. In addition, the mutations of ARHGAP32 gene down regulates Rac1, RhoA and CDC42, which cause podocyte damage, affect glomerular filtration barrier, cause proteinuria, and even cause kidney damage, even develop into FSGS. The mechanism of podocyte damage caused by mutations of ARHGAP32 gene was preliminarily discussed.