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In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis
- Source :
- Kidney International Reports, Kidney International Reports, Vol 4, Iss 9, Pp 1312-1322 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Introduction: Mutations in genes encoding nucleoporins (NUPs; components of nuclear pore complexes [NPCs]), such as NUP93, have been reported to cause steroid-resistant nephrotic syndrome (SRNS) or focal segmental glomerulosclerosis (FSGS), which often progresses to end-stage renal disease (ESRD) in childhood. The expression of NUP93 in renal or extrarenal tissues, and the mechanism by which NUP93 mutations cause this renal phenotype, remain unclear. Methods: The expression of NUP93 in normal control kidney and in a patient with FSGS carrying NUP93 mutations was examined by immunofluorescence analysis. The expression of NUP93 in blood cells was analyzed by Western blot analysis. Results: Immunofluorescence analysis detected NUP93 expression in nuclei of all glomerular and tubulointerstitial cells in human kidneys. Whole-exome sequencing identified a compound heterozygous NUP93 mutation comprising a novel missense mutation p.Arg525Trp, and a previously reported mutation, p.Tyr629Cys, in a patient with FSGS that developed ESRD at the age of 6 years. In the patient’s kidney, the intensity of NUP93 immunofluorescence was significantly decreased in the nuclei of both glomerular and extraglomerular cells. The expression of CD2-associated protein (CD2AP) and nephrin in the patient’s podocytes was relatively intact. The amount of NUP93 protein was not significantly altered in the peripheral blood mononuclear cells of the patient. Conclusion: NUP93 is expressed in the nuclei of all the cell types of the human kidney. Altered NUP93 expression in glomerular cells as well as extraglomerular cells by NUP93 mutations may underlie the pathogenic mechanism of SRNS or FSGS. Keywords: focal segmental glomerulosclerosis, nuclear pore complex, nucleoporin, NUP93, steroid-resistant nephrotic syndrome
- Subjects :
- Pathology
medicine.medical_specialty
030232 urology & nephrology
030204 cardiovascular system & hematology
lcsh:RC870-923
urologic and male genital diseases
medicine.disease_cause
Immunofluorescence
Nephrin
03 medical and health sciences
0302 clinical medicine
Focal segmental glomerulosclerosis
nuclear pore complex
Translational Research
steroid-resistant nephrotic syndrome
medicine
Missense mutation
focal segmental glomerulosclerosis
Mutation
Kidney
medicine.diagnostic_test
biology
urogenital system
business.industry
nucleoporin
lcsh:Diseases of the genitourinary system. Urology
medicine.disease
Phenotype
female genital diseases and pregnancy complications
medicine.anatomical_structure
Nephrology
biology.protein
NUP93
business
Nephrotic syndrome
Subjects
Details
- ISSN :
- 24680249
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Kidney International Reports
- Accession number :
- edsair.doi.dedup.....75a6b3ab09954cdcbff92e946d6d99e9
- Full Text :
- https://doi.org/10.1016/j.ekir.2019.05.1157