Keap1 knockdown in melanocytes induces cell proliferation and survival via HO-1-associated β-catenin signaling

Ji Young Kim, Hemin Lee, Eun Jung Lee, Mikyoung Kim, Tae Gyun Kim, Hyoung Pyo Kim, Sang Ho Oh

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background Nrf2-Keap1 signaling pathway protects cells against photo-oxidative stress. Yet in recent works, its role in melanogenesis together with cell protection functions against oxidative stress has been gaining interest. However, its effect on melanogenesis still has contradictory results from different studies. Objective The aims of our study were to investigate the effect of Keap1 silencing in melanocyte on melanogenesis and its associated mechanism. Methods Primary human epidermal melanocytes and melan-a cell line were used for this experiment. RNA sequencing was done to identify genes involved in melanocyte biology using Keap1 knockdown through siRNA techniques. And melanogenesis and the expression of melanogenesis-associated molecules were evaluated in Keap1 silenced melanocyte to examine the effects of Keap1 on melanogenesis, melanocyte growth, and related pathways. Results RNA-sequencing data revealed that Keap1 knockdown in primary human epidermal melanocytes (PHEMs) induced cell survival-related gene expression. Additionally, siRNA-mediated inhibition of Keap1 led to upregulation of MITF and melanogenesis-associated molecules along with Nrf2 activation in PHEMs. HO-1, a major gene that is upregulated in RNA-sequencing using Keap1-silenced PHEMs, protected melanocytes against H2O2-induced cell death and upregulated MITF and β-catenin expression. Further, increased expression of melanogenesis-associated molecules after Keap1 silencing was validated to occur through HO-1-associated β-catenin activation in a Keap1 and HO-1 double knockdown experiment. Conclusion This work suggests that Keap1 silencing in melanocytes induced melanogenesis and the expression of melanogenesis-associated molecules through HO-1-associated β-catenin activation. Keap1 downregulation in melanocytes is important for cell proliferation and survival.

Original languageEnglish
Pages (from-to)85-95
Number of pages11
JournalJournal of Dermatological Science
Volume88
Issue number1
DOIs
Publication statusPublished - 2017 Oct

Fingerprint

Catenins
Melanocytes
Cell proliferation
Cell Survival
Cell Proliferation
Molecules
Oxidative stress
Chemical activation
RNA
Small Interfering RNA
Genes
Cells
RNA Sequence Analysis
Cell death
Gene expression
Experiments
Oxidative Stress
Cytoprotection
Cell Death
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Kim, Ji Young ; Lee, Hemin ; Lee, Eun Jung ; Kim, Mikyoung ; Kim, Tae Gyun ; Kim, Hyoung Pyo ; Oh, Sang Ho. / Keap1 knockdown in melanocytes induces cell proliferation and survival via HO-1-associated β-catenin signaling. In: Journal of Dermatological Science. 2017 ; Vol. 88, No. 1. pp. 85-95.
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title = "Keap1 knockdown in melanocytes induces cell proliferation and survival via HO-1-associated β-catenin signaling",
abstract = "Background Nrf2-Keap1 signaling pathway protects cells against photo-oxidative stress. Yet in recent works, its role in melanogenesis together with cell protection functions against oxidative stress has been gaining interest. However, its effect on melanogenesis still has contradictory results from different studies. Objective The aims of our study were to investigate the effect of Keap1 silencing in melanocyte on melanogenesis and its associated mechanism. Methods Primary human epidermal melanocytes and melan-a cell line were used for this experiment. RNA sequencing was done to identify genes involved in melanocyte biology using Keap1 knockdown through siRNA techniques. And melanogenesis and the expression of melanogenesis-associated molecules were evaluated in Keap1 silenced melanocyte to examine the effects of Keap1 on melanogenesis, melanocyte growth, and related pathways. Results RNA-sequencing data revealed that Keap1 knockdown in primary human epidermal melanocytes (PHEMs) induced cell survival-related gene expression. Additionally, siRNA-mediated inhibition of Keap1 led to upregulation of MITF and melanogenesis-associated molecules along with Nrf2 activation in PHEMs. HO-1, a major gene that is upregulated in RNA-sequencing using Keap1-silenced PHEMs, protected melanocytes against H2O2-induced cell death and upregulated MITF and β-catenin expression. Further, increased expression of melanogenesis-associated molecules after Keap1 silencing was validated to occur through HO-1-associated β-catenin activation in a Keap1 and HO-1 double knockdown experiment. Conclusion This work suggests that Keap1 silencing in melanocytes induced melanogenesis and the expression of melanogenesis-associated molecules through HO-1-associated β-catenin activation. Keap1 downregulation in melanocytes is important for cell proliferation and survival.",
author = "Kim, {Ji Young} and Hemin Lee and Lee, {Eun Jung} and Mikyoung Kim and Kim, {Tae Gyun} and Kim, {Hyoung Pyo} and Oh, {Sang Ho}",
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Keap1 knockdown in melanocytes induces cell proliferation and survival via HO-1-associated β-catenin signaling. / Kim, Ji Young; Lee, Hemin; Lee, Eun Jung; Kim, Mikyoung; Kim, Tae Gyun; Kim, Hyoung Pyo; Oh, Sang Ho.

In: Journal of Dermatological Science, Vol. 88, No. 1, 10.2017, p. 85-95.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Keap1 knockdown in melanocytes induces cell proliferation and survival via HO-1-associated β-catenin signaling

AU - Kim, Ji Young

AU - Lee, Hemin

AU - Lee, Eun Jung

AU - Kim, Mikyoung

AU - Kim, Tae Gyun

AU - Kim, Hyoung Pyo

AU - Oh, Sang Ho

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N2 - Background Nrf2-Keap1 signaling pathway protects cells against photo-oxidative stress. Yet in recent works, its role in melanogenesis together with cell protection functions against oxidative stress has been gaining interest. However, its effect on melanogenesis still has contradictory results from different studies. Objective The aims of our study were to investigate the effect of Keap1 silencing in melanocyte on melanogenesis and its associated mechanism. Methods Primary human epidermal melanocytes and melan-a cell line were used for this experiment. RNA sequencing was done to identify genes involved in melanocyte biology using Keap1 knockdown through siRNA techniques. And melanogenesis and the expression of melanogenesis-associated molecules were evaluated in Keap1 silenced melanocyte to examine the effects of Keap1 on melanogenesis, melanocyte growth, and related pathways. Results RNA-sequencing data revealed that Keap1 knockdown in primary human epidermal melanocytes (PHEMs) induced cell survival-related gene expression. Additionally, siRNA-mediated inhibition of Keap1 led to upregulation of MITF and melanogenesis-associated molecules along with Nrf2 activation in PHEMs. HO-1, a major gene that is upregulated in RNA-sequencing using Keap1-silenced PHEMs, protected melanocytes against H2O2-induced cell death and upregulated MITF and β-catenin expression. Further, increased expression of melanogenesis-associated molecules after Keap1 silencing was validated to occur through HO-1-associated β-catenin activation in a Keap1 and HO-1 double knockdown experiment. Conclusion This work suggests that Keap1 silencing in melanocytes induced melanogenesis and the expression of melanogenesis-associated molecules through HO-1-associated β-catenin activation. Keap1 downregulation in melanocytes is important for cell proliferation and survival.

AB - Background Nrf2-Keap1 signaling pathway protects cells against photo-oxidative stress. Yet in recent works, its role in melanogenesis together with cell protection functions against oxidative stress has been gaining interest. However, its effect on melanogenesis still has contradictory results from different studies. Objective The aims of our study were to investigate the effect of Keap1 silencing in melanocyte on melanogenesis and its associated mechanism. Methods Primary human epidermal melanocytes and melan-a cell line were used for this experiment. RNA sequencing was done to identify genes involved in melanocyte biology using Keap1 knockdown through siRNA techniques. And melanogenesis and the expression of melanogenesis-associated molecules were evaluated in Keap1 silenced melanocyte to examine the effects of Keap1 on melanogenesis, melanocyte growth, and related pathways. Results RNA-sequencing data revealed that Keap1 knockdown in primary human epidermal melanocytes (PHEMs) induced cell survival-related gene expression. Additionally, siRNA-mediated inhibition of Keap1 led to upregulation of MITF and melanogenesis-associated molecules along with Nrf2 activation in PHEMs. HO-1, a major gene that is upregulated in RNA-sequencing using Keap1-silenced PHEMs, protected melanocytes against H2O2-induced cell death and upregulated MITF and β-catenin expression. Further, increased expression of melanogenesis-associated molecules after Keap1 silencing was validated to occur through HO-1-associated β-catenin activation in a Keap1 and HO-1 double knockdown experiment. Conclusion This work suggests that Keap1 silencing in melanocytes induced melanogenesis and the expression of melanogenesis-associated molecules through HO-1-associated β-catenin activation. Keap1 downregulation in melanocytes is important for cell proliferation and survival.

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