College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, PR China.
Genomic Research Center, EBIOGEN Inc, Seoul, Korea.
J Biomol Struct Dyn. 2021 Apr;39(6):2133-2151. doi: 10.1080/07391102.2020.1745281. Epub 2020 Apr 7.
The function of acetaldehyde dehydrogenase 1 (ALDH1) has been gradually elucidated in several diseases, especially in various cancers. However, the role of ALDH1 in skin-related diseases has been mostly unknown. Previously, we found that ALDH1 is involved in the pathogenesis of atopic dermatitis (AD). In this study, we used high-throughput screening (HTS) approaches to identify critical factors associated with ALDH1 in human keratinocytes to reveal its functions in skin. We overexpressed ALDH1 in human HaCaT keratinocytes and then conducted serial HTS studies, a DNA microarray and antibody array integrated with bioinformatics algorithms. Together, those tests identified several novel genes associated with the function of ALDH1 in keratinocytes, as well as AD, including CTSG and CCL11. In particular, GNB3, GHSR, TAS2R9, FFAR1, TAS2R16, CCL21, GPR32, NPFFR1, GPR15, FBXW12, CCL19, EDNRA, FFAR3, and RXFP3 proteins were consistently detected as hub proteins in the PPI maps. By integrating the datasets obtained from these HTS studies and using the strengths of each method, we obtained new insights into the functional role of ALDH1 in skin keratinocytes. The approach used here could contribute to the clinical understanding of ALDH1-associated applications for the treatment of AD.Communicated by Ramaswamy H. Sarma.
乙醛脱氢酶 1(ALDH1)的功能在几种疾病中逐渐得到阐明,尤其是在各种癌症中。然而,ALDH1 在皮肤相关疾病中的作用大多尚不清楚。之前,我们发现 ALDH1 参与了特应性皮炎(AD)的发病机制。在本研究中,我们使用高通量筛选(HTS)方法鉴定了与人类角质形成细胞中 ALDH1 相关的关键因素,以揭示其在皮肤中的功能。我们在人 HaCaT 角质形成细胞中过表达 ALDH1,然后进行了一系列 HTS 研究、DNA 微阵列和抗体阵列以及生物信息学算法的整合。这些测试共同确定了几个与角质形成细胞中 ALDH1 功能以及 AD 相关的新基因,包括 CTSG 和 CCL11。特别是,GNB3、GHSR、TAS2R9、FFAR1、TAS2R16、CCL21、GPR32、NPFFR1、GPR15、FBXW12、CCL19、EDNRA、FFAR3 和 RXFP3 蛋白被一致检测为 PPI 图谱中的枢纽蛋白。通过整合这些 HTS 研究获得的数据集,并利用每种方法的优势,我们对 ALDH1 在皮肤角质形成细胞中的功能作用有了新的认识。这里使用的方法可以为临床理解 ALDH1 相关的 AD 治疗应用提供帮助。