The Protective Role of KANK1 in Podocyte Injury

• Published in: International journal of molecular sciences Vol. 25; no. 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: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-06-2024; MDPI
• 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; Japan; KANK1; albuminuria; apoptosis; nephrotic syndrome; adriamycin; podocyte
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25115808

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.