Krüppel-like factor 15 is a key suppressor of podocyte fibrosis under rotational force-driven pressure

Mi Yeon Yu, Ji Eun Kim, Saram Lee, Jin Woo Choi, Yong Chul Kim, Seung Seok Han, Hajeong Lee, Ran Hui Cha, Jung Pyo Lee, Jae Wook Lee, Dong Ki Kim, Yon Su Kim, Seung Hee Yang

Research output: Contribution to journalArticle

Abstract

Krüppel-like factor 15 (KLF15) is a well-known transcription factor associated with podocyte injury and fibrosis. Recently, hypertensive nephropathy was discovered to be closely related to podocyte injury and fibrosis. However, methods to stimulate hypertension in vitro are lacking. Here, we constructed an in vitro model mimicking hypertension using a rotational force device to identify the role of KLF15 in fibrosis due to mechanically induced hypertensive injury. First, we found that KLF15 expression was decreased in patients with hypertensive nephropathy. Then, an in vitro study of hypertension due to rotational force was conducted, and an increase in fibrosis markers and decrease in KLF15 levels were determined after application of 4 mmHg pressure in primary cultured human podocytes. KLF15 and tight junction protein levels increased with retinoic acid treatment. siRNA-mediated inhibition of KLF15 exacerbated pressure-induced fibrosis injury, and KLF15 expression after treatment with angiotensin II was similar to that observed after treatment with the blood pressure modeling device. Furthermore, the reduced KLF15 levels after mechanical pressure application were restored after the administration of an antihypertensive drug. KLF15 expression was also low in vivo. We confirmed the protective role of KLF15 in fibrosis using a mechanically induced in vitro model of hypertensive injury.

Original languageEnglish
Article number111706
JournalExperimental Cell Research
Volume386
Issue number1
DOIs
StatePublished - 1 Jan 2020

Fingerprint

Podocytes
Fibrosis
Pressure
Wounds and Injuries
Hypertension
Tight Junction Proteins
Equipment and Supplies
Tretinoin
Angiotensin II
Antihypertensive Agents
Small Interfering RNA
Transcription Factors
Therapeutics
Blood Pressure
In Vitro Techniques

Keywords

  • Chronic kidney disease
  • Hypertension
  • KLF15
  • Nephropathy
  • Podocyte
  • Rotational force

Cite this

Yu, Mi Yeon ; Kim, Ji Eun ; Lee, Saram ; Choi, Jin Woo ; Kim, Yong Chul ; Han, Seung Seok ; Lee, Hajeong ; Cha, Ran Hui ; Lee, Jung Pyo ; Lee, Jae Wook ; Kim, Dong Ki ; Kim, Yon Su ; Yang, Seung Hee. / Krüppel-like factor 15 is a key suppressor of podocyte fibrosis under rotational force-driven pressure. In: Experimental Cell Research. 2020 ; Vol. 386, No. 1.
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Krüppel-like factor 15 is a key suppressor of podocyte fibrosis under rotational force-driven pressure. / Yu, Mi Yeon; Kim, Ji Eun; Lee, Saram; Choi, Jin Woo; Kim, Yong Chul; Han, Seung Seok; Lee, Hajeong; Cha, Ran Hui; Lee, Jung Pyo; Lee, Jae Wook; Kim, Dong Ki; Kim, Yon Su; Yang, Seung Hee.

In: Experimental Cell Research, Vol. 386, No. 1, 111706, 01.01.2020.

Research output: Contribution to journalArticle

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T1 - Krüppel-like factor 15 is a key suppressor of podocyte fibrosis under rotational force-driven pressure

AU - Yu, Mi Yeon

AU - Kim, Ji Eun

AU - Lee, Saram

AU - Choi, Jin Woo

AU - Kim, Yong Chul

AU - Han, Seung Seok

AU - Lee, Hajeong

AU - Cha, Ran Hui

AU - Lee, Jung Pyo

AU - Lee, Jae Wook

AU - Kim, Dong Ki

AU - Kim, Yon Su

AU - Yang, Seung Hee

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KW - KLF15

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