Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Protective Role of KANK1 in Podocyte Injury

Keiko Oda
,
Kan Katayama
* ,
Liqing Zang
,
Masaaki Toda
,
Akiko Tanoue
,
Ryosuke Saiki
,
Taro Yasuma
,
Corina N D'Alessandro-Gabazza
,
Yasuhito Shimada
ORCID logo ,
Mutsuki Mori
,
Yasuo Suzuki
,
Tomohiro Murata
,
Toshinori Hirai
,
Karl Tryggvason
,
Esteban C Gabazza
,
Kaoru Dohi
Version 1 : Received: 25 April 2024 / Approved: 25 April 2024 / Online: 25 April 2024 (16:53:56 CEST)

How to cite: Oda, K.; Katayama, K.; Zang, L.; Toda, M.; Tanoue, A.; Saiki, R.; Yasuma, T.; N D'Alessandro-Gabazza, C.; Shimada, Y.; Mori, M.; Suzuki, Y.; Murata, T.; Hirai, T.; Tryggvason, K.; C Gabazza, E.; Dohi, K. The Protective Role of KANK1 in Podocyte Injury. Preprints 2024, 2024041697. https://doi.org/10.20944/preprints202404.1697.v1 Oda, K.; Katayama, K.; Zang, L.; Toda, M.; Tanoue, A.; Saiki, R.; Yasuma, T.; N D'Alessandro-Gabazza, C.; Shimada, Y.; Mori, M.; Suzuki, Y.; Murata, T.; Hirai, T.; Tryggvason, K.; C Gabazza, E.; Dohi, K. The Protective Role of KANK1 in Podocyte Injury. Preprints 2024, 2024041697. https://doi.org/10.20944/preprints202404.1697.v1

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.

Keywords

adriamycin; albuminuria; apoptosis; KANK1; nephrotic syndrome; podocyte

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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