Rong Li1, Chen Huang2, Jeff Cheuk Hin Ho3, Cherry Chi Tim Leung3, Richard Yuen Chong Kong3, Yu Li1, Xiao Liang1, Keng Po Lai4, William Ka Fai Tse5. 1. Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Guilin, China; Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China. 2. The Center for Data Science in Health and Medicine, Business School, Qingdao University, Qingdao, Shandong Province, China. 3. Department of Chemistry, City University of Hong Kong, Hong Kong SAR. 4. Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Guilin, China; Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China; Department of Chemistry, City University of Hong Kong, Hong Kong SAR. Electronic address: kengplai@cityu.edu.hk. 5. Center for Promotion of International Education and Research, Faculty of Agriculture, Kyushu University, Fukuoka, Japan. Electronic address: kftse@agr.kyushu-u.ac.jp.
Abstract
OBJECTIVE: Cleft lip (CL) is a common congenital anomaly that can be syndromic or non-syndromic. It can be triggered by the mutation of gene or environmental factors. The incidence of CL is about 1 out of 700 live births. Facial development is a complex process, and there is no existing therapy to prevent the disease development. One of the characteristics in this facial malformation is the increased presence of reactive oxygen species (ROS). In this study, we hypothesize that the antioxidant glutathione (GSH) could help to attenuate the oxidative stress in this disease. METHODS: Bioinformatics network pharmacology was applied to determine pharmacological targets and molecular mechanisms of GSH treatment for CL. Moreover, RNA-sequencing of the POLR1C knockdown osteoblast CL model was applied to validate the in silico data of using GSH in CL. RESULTS: Twenty-two core targets of GSH and CL were identified via various bioinformatics tools. The GO and KEGG analysis indicated that GSH could modulate two major families (matrix metalloproteinase and integrins), which are related to extracellular matrix modification and composition for facial development in CL. The findings from POLR1C knockdown model further supported the rescue response of GSH in CL. CONCLUSIONS: The study uncovered the possible pharmacological mechanism of GSH for treating CL. The data helps research group to focus on the specific pathways for understanding the biological action of GSH for treating the CL in the future.
OBJECTIVE:Cleft lip (CL) is a common congenital anomaly that can be syndromic or non-syndromic. It can be triggered by the mutation of gene or environmental factors. The incidence of CL is about 1 out of 700 live births. Facial development is a complex process, and there is no existing therapy to prevent the disease development. One of the characteristics in this facial malformation is the increased presence of reactive oxygen species (ROS). In this study, we hypothesize that the antioxidant glutathione (GSH) could help to attenuate the oxidative stress in this disease. METHODS: Bioinformatics network pharmacology was applied to determine pharmacological targets and molecular mechanisms of GSH treatment for CL. Moreover, RNA-sequencing of the POLR1C knockdown osteoblast CL model was applied to validate the in silico data of using GSH in CL. RESULTS: Twenty-two core targets of GSH and CL were identified via various bioinformatics tools. The GO and KEGG analysis indicated that GSH could modulate two major families (matrix metalloproteinase and integrins), which are related to extracellular matrix modification and composition for facial development in CL. The findings from POLR1C knockdown model further supported the rescue response of GSH in CL. CONCLUSIONS: The study uncovered the possible pharmacological mechanism of GSH for treating CL. The data helps research group to focus on the specific pathways for understanding the biological action of GSH for treating the CL in the future.
Authors: Chi Tim Leung; Yi Yang; Kwan Ngok Yu; Nathan Tam; Ting Fung Chan; Xiao Lin; Richard Yuen Chong Kong; Jill Man Ying Chiu; Alice Sze Tsai Wong; Wing Yee Lui; Karen Wing Yee Yuen; Keng Po Lai; Rudolf Shiu Sun Wu Journal: Front Genet Date: 2021-08-02 Impact factor: 4.599