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

• Published in: Journal of inflammation research Vol. 14; pp. 4299 - 4312
• Main Authors: Jang, Soyeon, Jang, Soyoung, Kim, Si-Yong, Ko, Jiwon, Kim, Eungyung, Park, Ji Yeong, Hyung, Hyejin, Lee, Jin Hong, Lim, Su-Geun, Park, Sijun, Yi, Junkoo, Lee, Heon-Jin, Kim, Myoung Ok, Lee, Hyun-Shik, Ryoo, Zae Young
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2021; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Analysis; Angiogenesis; Antiviral drugs; Biotechnology; Cell growth; Cell lines; Chemokines; Cytokines; Cytomegalovirus; Dermis; Extracellular signal-regulated kinase; Gene expression; Genetic aspects; Genetic engineering; Imiquimod; Inflammation; Interleukin 6; Interleukins; Keratin; keratinocyte; Keratinocytes; Kinases; Laboratory animals; let-7; lin28a; Medical research; Medicine, Experimental; MicroRNA; MicroRNAs; miRNA; Original Research; Phenotypes; Plaques; Psoriasis; Reagents; Skin; Skin diseases; Stem cells; Transcription; Transgenic mice; Tumor necrosis factor-TNF; South Korea; United States > US; Lin28a; let-7; keratinocyte; psoriasis
• ISSN: 1178-7031; 1178-7031
• DOI: 10.2147/JIR.S312963

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
and psoriasis progression, which promoted the pathological characteristic of psoriasis in epidermal keratinocytes.
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.
In vivo and in vitro results revealed that overexpression of
downregulated microRNA let-7 expression levels and caused hyperproliferation and abnormal differentiation in keratinocytes. In imiquimod (IMQ)-induced psoriasis-like inflammation,
overexpressing transgenic (TG) mice exhibited more severe symptoms of psoriasis.
Mechanistically,
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).