Loss of KLF15 accelerates chronic podocyte injury

Han,Seung Seok; Yu,Mi‑Yeon; Yoo,Kyung Don; Lee,Jung Pyo; Kim,Dong Ki; Kim,Yon Su; Yang,Seung Hee

doi:10.3892/ijmm.2018.3726

Loss of KLF15 accelerates chronic podocyte injury

Authors:
- Seung Seok Han
- Mi‑Yeon Yu
- Kyung Don Yoo
- Jung Pyo Lee
- Dong Ki Kim
- Yon Su Kim
- Seung Hee Yang
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Affiliations: Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea, Department of Internal Medicine, Dongguk University College of Medicine, Gyeongju, Gyeongsangbuk‑do 13620, Republic of Korea, Kidney Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
Published online on: June 11, 2018 https://doi.org/10.3892/ijmm.2018.3726
Pages: 1593-1602

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Abstract

Krüppel‑like factor 15 (KLF15), also known as kidney‑enriched transcription factor, is known to participate in podocyte differentiation. However, the role of KLF15 in chronic podocyte injury remains incompletely understood, particularly in proteinuric disease models. In the present study, the 5/6 nephrectomy mouse model was used to induce chronic podocyte injury. Human primary podocytes were isolated by flow cytometry and cultured to emulate the injury process in an in vitro system. Biopsied kidney tissue samples were obtained from patients with primary membranous nephropathy or diabetic nephropathy in order to analyze the relationship between glomerular KLF15 expression and subsequent outcomes. When 5/6 nephrectomy was predisposed to progressive kidney damage, fibrosis markers increased, while podocyte KLF15 expression decreased. In addition, increased fibrosis marker expression in human primary podocytes following treatment with transforming growth factor‑β was aggravated by the knockdown of KLF15. These trends were reversed after cultured podocytes were treated with cyclosporine. When patients were grouped according to KLF15 expression levels in kidney tissue, the low expression groups were demonstrated to have worse renal outcomes, such as non‑remission of disease and end‑stage renal disease. In conclusion, the present findings revealed that low expression of KLF15 was associated with chronic podocyte injury.

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