Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes

Soyeon Jang,1 Soyoung Jang,1 Si-Yong Kim,1 Jiwon Ko,1 Eungyung Kim,2 Ji Yeong Park,1 Hyejin Hyung,1 Jin Hong Lee,1 Su-Geun Lim,3 Sijun Park,3 Junkoo Yi,4 Heon-Jin Lee,5 Myoung Ok Kim,2 Hyun-Shik Lee,1 Zae Young Ryoo1 1School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook Natio...

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Autores principales:	Jang S, Kim SY, Ko J, Kim E, Park JY, Hyung H, Lee JH, Lim SG, Park S, Yi J, Lee HJ, Kim MO, Lee HS, Ryoo ZY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	psoriasis keratinocyte lin28a let-7 Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/69c9d0a399dc439182d99918604cd687
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spelling	oai:doaj.org-article:69c9d0a399dc439182d99918604cd6872021-12-02T15:12:56ZOverexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes1178-7031https://doaj.org/article/69c9d0a399dc439182d99918604cd6872021-08-01T00:00:00Zhttps://www.dovepress.com/overexpression-of-lin28a-aggravates-psoriasis-like-phenotype-by-regula-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Soyeon Jang,1 Soyoung Jang,1 Si-Yong Kim,1 Jiwon Ko,1 Eungyung Kim,2 Ji Yeong Park,1 Hyejin Hyung,1 Jin Hong Lee,1 Su-Geun Lim,3 Sijun Park,3 Junkoo Yi,4 Heon-Jin Lee,5 Myoung Ok Kim,2 Hyun-Shik Lee,1 Zae Young Ryoo1 1School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea; 2Department of Animal Science and Biotechnology, Kyungpook National University, Daegu, Korea; 3School of Life Science, Kyungpook National University, Daegu, Korea; 4Gyeongsangbukdo Livestock Research Institute, Yeongju, Korea; 5Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, 41940, KoreaCorrespondence: Zae Young Ryoo; Hyun-Shik LeeSchool of Life Science, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, KoreaTel +82-53-950-7361; +82-53-950-7367Fax +82-53-943-6925; +82-53-943-2762Email jaewoong64@knu.ac.kr; leeh@knu.ac.krPurpose: Psoriasis is a common and well-studied autoimmune skin disease, which is characterized by plaques. The formation of psoriasis plaques occurs through the hyperproliferation and abnormal differentiation of keratinocytes, infiltration of numerous immune cells into the dermis, increased subepidermal angiogenesis, and various autoimmune-associated cytokines and chemokines. According to previous research, Lin28 regulates the let-7 family, and let-7b is associated with psoriasis. However, the link between Lin28 and psoriasis is unclear. In this study, an association was identified between Lin28a and psoriasis progression, which promoted the pathological characteristic of psoriasis in epidermal keratinocytes.Patients and Methods: This study aims to investigate the role of Lin28a and its underlying mechanism in psoriasis through in vivo and in vitro models, which include the Lin28a-overexpressing transgenic (TG) mice and Lin28a-overexpressing human keratinocyte (HaCaT) cell lines, respectively.Results: In vivo and in vitro results revealed that overexpression of Lin28a downregulated microRNA let-7 expression levels and caused hyperproliferation and abnormal differentiation in keratinocytes. In imiquimod (IMQ)-induced psoriasis-like inflammation, Lin28a overexpressing transgenic (TG) mice exhibited more severe symptoms of psoriasis.Conclusion: Mechanistically, Lin28a exacerbated psoriasis-like inflammation through the activation of the extracellular-signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 signaling (STAT 3) by targeting proinflammatory cytokine interleukin-6 (IL-6).Keywords: psoriasis, keratinocyte, Lin28a, let-7Jang SJang SKim SYKo JKim EPark JYHyung HLee JHLim SGPark SYi JLee HJKim MOLee HSRyoo ZYDove Medical Pressarticlepsoriasiskeratinocytelin28alet-7PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4299-4312 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	psoriasis keratinocyte lin28a let-7 Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	psoriasis keratinocyte lin28a let-7 Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Jang S Jang S Kim SY Ko J Kim E Park JY Hyung H Lee JH Lim SG Park S Yi J Lee HJ Kim MO Lee HS Ryoo ZY Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes
description	Soyeon Jang,1 Soyoung Jang,1 Si-Yong Kim,1 Jiwon Ko,1 Eungyung Kim,2 Ji Yeong Park,1 Hyejin Hyung,1 Jin Hong Lee,1 Su-Geun Lim,3 Sijun Park,3 Junkoo Yi,4 Heon-Jin Lee,5 Myoung Ok Kim,2 Hyun-Shik Lee,1 Zae Young Ryoo1 1School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea; 2Department of Animal Science and Biotechnology, Kyungpook National University, Daegu, Korea; 3School of Life Science, Kyungpook National University, Daegu, Korea; 4Gyeongsangbukdo Livestock Research Institute, Yeongju, Korea; 5Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, 41940, KoreaCorrespondence: Zae Young Ryoo; Hyun-Shik LeeSchool of Life Science, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, KoreaTel +82-53-950-7361; +82-53-950-7367Fax +82-53-943-6925; +82-53-943-2762Email jaewoong64@knu.ac.kr; leeh@knu.ac.krPurpose: Psoriasis is a common and well-studied autoimmune skin disease, which is characterized by plaques. The formation of psoriasis plaques occurs through the hyperproliferation and abnormal differentiation of keratinocytes, infiltration of numerous immune cells into the dermis, increased subepidermal angiogenesis, and various autoimmune-associated cytokines and chemokines. According to previous research, Lin28 regulates the let-7 family, and let-7b is associated with psoriasis. However, the link between Lin28 and psoriasis is unclear. In this study, an association was identified between Lin28a and psoriasis progression, which promoted the pathological characteristic of psoriasis in epidermal keratinocytes.Patients and Methods: This study aims to investigate the role of Lin28a and its underlying mechanism in psoriasis through in vivo and in vitro models, which include the Lin28a-overexpressing transgenic (TG) mice and Lin28a-overexpressing human keratinocyte (HaCaT) cell lines, respectively.Results: In vivo and in vitro results revealed that overexpression of Lin28a downregulated microRNA let-7 expression levels and caused hyperproliferation and abnormal differentiation in keratinocytes. In imiquimod (IMQ)-induced psoriasis-like inflammation, Lin28a overexpressing transgenic (TG) mice exhibited more severe symptoms of psoriasis.Conclusion: Mechanistically, Lin28a exacerbated psoriasis-like inflammation through the activation of the extracellular-signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 signaling (STAT 3) by targeting proinflammatory cytokine interleukin-6 (IL-6).Keywords: psoriasis, keratinocyte, Lin28a, let-7
format	article
author	Jang S Jang S Kim SY Ko J Kim E Park JY Hyung H Lee JH Lim SG Park S Yi J Lee HJ Kim MO Lee HS Ryoo ZY
author_facet	Jang S Jang S Kim SY Ko J Kim E Park JY Hyung H Lee JH Lim SG Park S Yi J Lee HJ Kim MO Lee HS Ryoo ZY
author_sort	Jang S
title	Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes
title_short	Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes
title_full	Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes
title_fullStr	Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes
title_full_unstemmed	Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes
title_sort	overexpression of lin28a aggravates psoriasis-like phenotype by regulating the proliferation and differentiation of keratinocytes
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/69c9d0a399dc439182d99918604cd687
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Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes

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