The Protective Role of KANK1 in Podocyte Injury

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific knockout mice were g...

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Bibliographic Details
Published in:International journal of molecular sciences 2024-06, Vol.25 (11), p.5808
Main Authors: Oda, Keiko, Katayama, Kan, Zang, Liqing, Toda, Masaaki, Tanoue, Akiko, Saiki, Ryosuke, Yasuma, Taro, D'Alessandro-Gabazza, Corina N, Shimada, Yasuhito, Mori, Mutsuki, Suzuki, Yasuo, Murata, Tomohiro, Hirai, Toshinori, Tryggvason, Karl, Gabazza, Esteban C, Dohi, Kaoru
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
adriamycin
albuminuria
Animals
Anthracyclines
Apoptosis
Chronic kidney failure
Creatinine
Cytoskeletal Proteins - genetics
Cytoskeletal Proteins - metabolism
Doxorubicin
Genes
Humans
KANK1
Kidney diseases
Localization
Male
Medicin och hälsovetenskap
Mice
Mice, Knockout
Mutation
nephrotic syndrome
Nephrotic Syndrome - genetics
Nephrotic Syndrome - metabolism
Nephrotic Syndrome - pathology
podocyte
Podocytes - metabolism
Podocytes - pathology
Proteins
Steroids
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
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Summary:Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, -deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25115808