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
School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea.
Department of Animal Science and Biotechnology, Kyungpook National University, Daegu, Korea.
J Inflamm Res. 2021 Aug 30;14:4299-4312. doi: 10.2147/JIR.S312963. eCollection 2021.
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).
银屑病是一种常见且研究充分的自身免疫性皮肤病，其特征为斑块。银屑病斑块的形成是通过角质形成细胞的过度增殖和异常分化、大量免疫细胞浸润至真皮、表皮下血管生成增加以及各种自身免疫相关的细胞因子和趋化因子实现的。根据先前研究，Lin28调节let-7家族，且let-7b与银屑病相关。然而，Lin28与银屑病之间的联系尚不清楚。在本研究中，确定了[具体内容缺失]与银屑病进展之间的关联，其促进了表皮角质形成细胞中银屑病的病理特征。
本研究旨在通过体内和体外模型研究Lin28a在银屑病中的作用及其潜在机制，体内模型为过表达Lin28a的转基因（TG）小鼠，体外模型为过表达Lin28a的人角质形成细胞（HaCaT）细胞系。
体内和体外结果显示，[具体内容缺失]的过表达下调了微小RNA let-7的表达水平，并导致角质形成细胞过度增殖和异常分化。在咪喹莫特（IMQ）诱导的银屑病样炎症中，过表达[具体内容缺失]的转基因（TG）小鼠表现出更严重的银屑病症状。
机制上，[具体内容缺失]通过靶向促炎细胞因子白细胞介素-6（IL-6）激活细胞外信号调节激酶（ERK）和信号转导及转录激活因子3信号通路（STAT 3），加剧了银屑病样炎症。
