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Int J Biol Macromol. 2019 Jul 15;133:391-411. doi: 10.1016/j.ijbiomac.2019.04.039. Epub 2019 Apr 8.

An OMICS-based study of the role of C3dg in keratinocytes: RNA sequencing, antibody-chip array, and bioinformatics approaches.

Author information

1
College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, 315100, PR China.
2
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
3
Genomics Research Center, EBIOGEN Inc., Seoul 07282, Republic of Korea.
4
Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul 135-710, Republic of Korea.
5
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea. Electronic address: jaerin@skku.edu.
6
College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, 315100, PR China; Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul 135-710, Republic of Korea; Skin Diseases Research Center, Yangtze Delta Region Institute of Tsinghua University, 705 Yatai Road, Jiaxing 314006, PR China. Electronic address: parkyd@hotmail.com.

Abstract

Previously, we have identified the C3dg protein as an important player in the pathogenesis of atopic dermatitis (AD). In this study, we aimed to identify critical factors associated with C3dg in human keratinocytes based on high-throughput screening (HTS) approaches. We overexpressed C3dg in HaCaT human keratinocytes and conducted serial HTS studies, including RNA sequencing analysis integrated with antibody-chip arrays and implementation of bioinformatics algorithms (PPI mappings). Cumulatively, these approaches identified several novel C3dg-associated genes and proteins that are thought to be significantly involved in skin diseases including AD. These novel genes and proteins included LPA, PROZ, BLK, CLDN11, and FGF22, which are believed to play important roles in C3dg-associated skin functions in keratinocytes, as well as genes related to the two important pathways of systemic lupus erythematosus and Staphylococcus aureus infection. In particular, FGF22 is a unique gene that was detected and validated in all methods applied in this study. By integrating the datasets obtained from these HTS studies and utilizing the strengths of each method, we obtained new insights into the functional role of C3dg in keratinocytes. The approach used here contributes to clinical understanding of C3dg-associated applications and may also be applicable to treatment of AD.

KEYWORDS:

C3dg; Keratinocytes; Microarray

PMID:
30974145
DOI:
10.1016/j.ijbiomac.2019.04.039
[Indexed for MEDLINE]

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