In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Kidney International Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024919313579 |
| _version_ | 1819319195123318784 |
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| author | Taeko Hashimoto Yutaka Harita Keiichi Takizawa Seiya Urae Kiyonobu Ishizuka Kenichiro Miura Shigeru Horita Daisuke Ogino Gen Tamiya Hideki Ishida Tetsuo Mitsui Kiyoshi Hayasaka Motoshi Hattori |
| author_facet | Taeko Hashimoto Yutaka Harita Keiichi Takizawa Seiya Urae Kiyonobu Ishizuka Kenichiro Miura Shigeru Horita Daisuke Ogino Gen Tamiya Hideki Ishida Tetsuo Mitsui Kiyoshi Hayasaka Motoshi Hattori |
| author_sort | Taeko Hashimoto |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-24T10:59:49Z |
| format | Article |
| id | doaj.art-41e6a07eedce4ec9a065f923faba22bd |
| institution | Directory Open Access Journal |
| issn | 2468-0249 |
| language | English |
| last_indexed | 2024-12-24T10:59:49Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj.art-41e6a07eedce4ec9a065f923faba22bd2022-12-21T16:58:45ZengElsevierKidney International Reports2468-02492019-09-014913121322In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental GlomerulosclerosisTaeko Hashimoto0Yutaka Harita1Keiichi Takizawa2Seiya Urae3Kiyonobu Ishizuka4Kenichiro Miura5Shigeru Horita6Daisuke Ogino7Gen Tamiya8Hideki Ishida9Tetsuo Mitsui10Kiyoshi Hayasaka11Motoshi Hattori12Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan; Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Correspondence: Yutaka Harita, Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan.Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, JapanDepartment of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, JapanDepartment of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, JapanDepartment of Pediatrics, Yamagata University School of Medicine, Yamagata, JapanTohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; RIKEN Center for Advanced Intelligence Project, Tokyo, JapanDepartment of Urology, Tokyo Women's Medical University, School of Medicine, Tokyo, JapanDepartment of Pediatrics, Yamagata University School of Medicine, Yamagata, JapanDepartment of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan; Department of Pediatrics, Miyukikai Hospital, Kaminoyama, JapanDepartment of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, JapanIntroduction: 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 syndromehttp://www.sciencedirect.com/science/article/pii/S2468024919313579 |
| spellingShingle | Taeko Hashimoto Yutaka Harita Keiichi Takizawa Seiya Urae Kiyonobu Ishizuka Kenichiro Miura Shigeru Horita Daisuke Ogino Gen Tamiya Hideki Ishida Tetsuo Mitsui Kiyoshi Hayasaka Motoshi Hattori In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis Kidney International Reports |
| title | In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis |
| title_full | In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis |
| title_fullStr | In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis |
| title_full_unstemmed | In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis |
| title_short | In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis |
| title_sort | in vivo expression of nup93 and its alteration by nup93 mutations causing focal segmental glomerulosclerosis |
| url | http://www.sciencedirect.com/science/article/pii/S2468024919313579 |
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