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Regulation of pro-opiomelanocortin (POMC) gene transcription by interleukin-31 via early growth response 1 (EGR-1) in HaCaT keratinocytes
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Regulation of pro-opiomelanocortin (POMC) gene transcription by interleukin-31 via early growth response 1 (EGR-1) in HaCaT keratinocytes
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Regulation of pro-opiomelanocortin (POMC) gene transcription by interleukin-31 via early growth response 1 (EGR-1) in HaCaT keratinocytes
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Journal Article
Regulation of pro-opiomelanocortin (POMC) gene transcription by interleukin-31 via early growth response 1 (EGR-1) in HaCaT keratinocytes
2020
Overview
Pro-opiomelanocortin (POMC) is a large precursor protein of and β-endorphin. POMC expressed in keratinocytes regulates various pathophysiological responses, such as pruritus in atopic dermatitis. Interleukin (IL)-31 is a T helper 2 (Th2)-derived cytokine that functions as a pruritogen, stimulating the sensory neurons in the skin. However, the regulatory mechanism underlying IL-31-induced
POMC
expression in keratinocytes remains largely unknown. Herein, using a 5′-serial deletion and site-specific mutation constructs of the regulatory region of
POMC
, we demonstrated that a putative EGR1-binding sequence (EBS) motif in
POMC
is required for its upregulation by IL-31 in HaCaT keratinocytes. Notably, EGR-1 directly interacted with the EBS motif in
POMC
. The ectopic expression of EGR-1 stimulated the
POMC
promoter activity, whereas the knockdown of
EGR-1
expression by RNA interference reduced IL-31-induced
POMC
expression. Furthermore, we observed that three major mitogen-activated protein kinases, ERK, JNK, and p38 kinase, mediated IL-31-induced
EGR-1
expression. In summary, our results suggest that EGR-1
trans
-activates
POMC
in response to IL-31 stimulation in HaCaT keratinocytes.
Publisher
Springer Netherlands,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ Early Growth Response Protein 1 - antagonists & inhibitors
/ Early Growth Response Protein 1 - genetics
/ Early Growth Response Protein 1 - physiology
/ Extracellular signal-regulated kinase
/ Humans
/ Kinases
/ MAP Kinase Signaling System - drug effects
/ mitogen-activated protein kinase
/ mutation
/ Pro-Opiomelanocortin - biosynthesis
/ Pro-Opiomelanocortin - genetics
/ Promoter Regions, Genetic - genetics
/ Pruritus
/ Real-Time Polymerase Chain Reaction
/ Recombinant Proteins - biosynthesis
/ Recombinant Proteins - genetics
/ RNA, Small Interfering - genetics
/ RNA, Small Interfering - pharmacology
