Inhibition of yes-associated protein by verteporfin ameliorates unilateral ureteral obstruction-induced renal tubulointerstitial inflammation and fibrosis

Jixiu Jin; Tian Wang; Woong Park; Wenjia Li; Won Kim; Sung Kwang Park; Kyung Pyo Kang

doi:10.3390/ijms21218184

Inhibition of yes-associated protein by verteporfin ameliorates unilateral ureteral obstruction-induced renal tubulointerstitial inflammation and fibrosis

Jixiu Jin
, Tian Wang
, Woong Park
, Wenjia Li
, Won Kim
, Sung Kwang Park^*
, Kyung Pyo Kang

^*Corresponding author for this work

Department of Medicine

Jeonbuk National University

Research output: Contribution to journal › Journal article › peer-review

34 Scopus citations

Abstract

Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-β1/Smad signaling pathway.

Original language	English
Article number	8184
Pages (from-to)	1-15
Number of pages	15
Journal	International Journal of Molecular Sciences
Volume	21
Issue number	21
DOIs	https://doi.org/10.3390/ijms21218184
State	Published - 2020.11.1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Extracellular matrix
Hippo pathway
Inflammation
Kidney fibrosis
Myofibroblast activation
Verteporfin

Quacquarelli Symonds(QS) Subject Topics

Computer Science & Information Systems
Engineering - Petroleum
Data Science
Engineering - Chemical
Chemistry
Biological Sciences

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10.3390/ijms21218184

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title = "Inhibition of yes-associated protein by verteporfin ameliorates unilateral ureteral obstruction-induced renal tubulointerstitial inflammation and fibrosis",

abstract = "Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-β1/Smad signaling pathway.",

keywords = "Extracellular matrix, Hippo pathway, Inflammation, Kidney fibrosis, Myofibroblast activation, Verteporfin",

author = "Jixiu Jin and Tian Wang and Woong Park and Wenjia Li and Won Kim and Park, \{Sung Kwang\} and Kang, \{Kyung Pyo\}",

note = "Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = nov,

day = "1",

doi = "10.3390/ijms21218184",

language = "English",

volume = "21",

pages = "1--15",

journal = "International Journal of Molecular Sciences",

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TY - JOUR

T1 - Inhibition of yes-associated protein by verteporfin ameliorates unilateral ureteral obstruction-induced renal tubulointerstitial inflammation and fibrosis

AU - Jin, Jixiu

AU - Wang, Tian

AU - Park, Woong

AU - Li, Wenjia

AU - Kim, Won

AU - Park, Sung Kwang

AU - Kang, Kyung Pyo

PY - 2020/11/1

Y1 - 2020/11/1

N2 - Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-β1/Smad signaling pathway.

AB - Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-β1/Smad signaling pathway.

KW - Extracellular matrix

KW - Hippo pathway

KW - Inflammation

KW - Kidney fibrosis

KW - Myofibroblast activation

KW - Verteporfin

UR - https://www.scopus.com/pages/publications/85094843562

U2 - 10.3390/ijms21218184

DO - 10.3390/ijms21218184

M3 - Journal article

C2 - 33142952

AN - SCOPUS:85094843562

SN - 1661-6596

VL - 21

SP - 1

EP - 15

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 21

M1 - 8184

ER -

Inhibition of yes-associated protein by verteporfin ameliorates unilateral ureteral obstruction-induced renal tubulointerstitial inflammation and fibrosis

Abstract

UN SDGs

Keywords

Quacquarelli Symonds(QS) Subject Topics

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