Oda, K.; Katayama, K.; Zang, L.; Toda, M.; Tanoue, A.; Saiki, R.; Yasuma, T.; D’Alessandro-Gabazza, C.N.; Shimada, Y.; Mori, M.; Suzuki, Y.; Murata, T.; Hirai, T.; Tryggvason, K.; Gabazza, E.C.; Dohi, K. The Protective Role of KANK1 in Podocyte Injury. Int. J. Mol. Sci.2024, 25, 5808.
Oda, K.; Katayama, K.; Zang, L.; Toda, M.; Tanoue, A.; Saiki, R.; Yasuma, T.; D’Alessandro-Gabazza, C.N.; Shimada, Y.; Mori, M.; Suzuki, Y.; Murata, T.; Hirai, T.; Tryggvason, K.; Gabazza, E.C.; Dohi, K. The Protective Role of KANK1 in Podocyte Injury. Int. J. Mol. Sci. 2024, 25, 5808.
Oda, K.; Katayama, K.; Zang, L.; Toda, M.; Tanoue, A.; Saiki, R.; Yasuma, T.; D’Alessandro-Gabazza, C.N.; Shimada, Y.; Mori, M.; Suzuki, Y.; Murata, T.; Hirai, T.; Tryggvason, K.; Gabazza, E.C.; Dohi, K. The Protective Role of KANK1 in Podocyte Injury. Int. J. Mol. Sci.2024, 25, 5808.
Oda, K.; Katayama, K.; Zang, L.; Toda, M.; Tanoue, A.; Saiki, R.; Yasuma, T.; D’Alessandro-Gabazza, C.N.; Shimada, Y.; Mori, M.; Suzuki, Y.; Murata, T.; Hirai, T.; Tryggvason, K.; Gabazza, E.C.; Dohi, K. The Protective Role of KANK1 in Podocyte Injury. Int. J. Mol. Sci. 2024, 25, 5808.
Abstract
Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 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 Kank1 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, KANK1-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.
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