Yanwei Xiang1, Le Kuai2, Yi Ru3, Jingsi Jiang3, Xin Li2, Fulun Li2, Qilong Chen4, Bin Li5. 1. Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. 2. Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. 3. Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. 4. Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: cqlw1975@126.com. 5. Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: 18930568129@163.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-ji Hua-yu (SJHY) formula is a traditional Chinese herbal which is effective in treating diabetic ulcers. It has been indicated to accelerate re-epithelialization and healing time of cutaneous wounds in a Streptozotocin (STZ)-induced diabetic mouse model. However, its mechanisms remain undetermined. AIM OF THE STUDY: To reveal the molecular mechanisms of SJHY formula in treating diabetic wounds through transcriptional profiling and circRNA-miRNA-mRNA network analysis clues. MATERIALS AND METHODS: Protein expressions of tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-1β in skin tissues of wounds from SJHY formula-treated and untreated mice were analyzed by Bio-Plex assay. Differentially expressed (DE) genes were detected by whole transcriptome sequencing (RNA-seq). Using predicted miRNA targets, circRNA-miRNA-mRNA networks were constructed. Furthermore, quantitative real-time PCR (qRT-PCR) was utilized to validate the circRNA-miRNA-mRNA networks. RESULTS: Bio-Plex assay illustrated that the protein expressions of TNF-α, IL-1β, IL-6 were down-regulated in SJHY formula-treated diabetic wounds compared with untreated wounds. RNA-seq identified 11 DE circRNAs and 476 DE mRNAs between SJHY formula-treated and diabetic mice, including 4 upregulated and 7 downregulated circRNAs, 311 upregulated and 165 downregulated mRNAs. CircRNA-Krt13/miR-665-3p/Itga3 and circRNA-Krt14/miR-706/Mylk4 pathways were built, which may contribute to the healing of SJHY formula-treated diabetic wounds. CONCLUSIONS: Overall, this study suggests that these 2 circRNA-miRNA-mRNA networks are potential biomarkers for evaluation of SJHY formula efficacy in diabetic wound healing, which provides evidence to support its clinical applications.
ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-ji Hua-yu (SJHY) formula is a traditional Chinese herbal which is effective in treating diabetic ulcers. It has been indicated to accelerate re-epithelialization and healing time of cutaneous wounds in a Streptozotocin (STZ)-induced diabeticmouse model. However, its mechanisms remain undetermined. AIM OF THE STUDY: To reveal the molecular mechanisms of SJHY formula in treating diabetic wounds through transcriptional profiling and circRNA-miRNA-mRNA network analysis clues. MATERIALS AND METHODS: Protein expressions of tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-1β in skin tissues of wounds from SJHY formula-treated and untreated mice were analyzed by Bio-Plex assay. Differentially expressed (DE) genes were detected by whole transcriptome sequencing (RNA-seq). Using predicted miRNA targets, circRNA-miRNA-mRNA networks were constructed. Furthermore, quantitative real-time PCR (qRT-PCR) was utilized to validate the circRNA-miRNA-mRNA networks. RESULTS: Bio-Plex assay illustrated that the protein expressions of TNF-α, IL-1β, IL-6 were down-regulated in SJHY formula-treated diabetic wounds compared with untreated wounds. RNA-seq identified 11 DE circRNAs and 476 DE mRNAs between SJHY formula-treated and diabeticmice, including 4 upregulated and 7 downregulated circRNAs, 311 upregulated and 165 downregulated mRNAs. CircRNA-Krt13/miR-665-3p/Itga3 and circRNA-Krt14/miR-706/Mylk4 pathways were built, which may contribute to the healing of SJHY formula-treated diabetic wounds. CONCLUSIONS: Overall, this study suggests that these 2 circRNA-miRNA-mRNA networks are potential biomarkers for evaluation of SJHY formula efficacy in diabetic wound healing, which provides evidence to support its clinical applications.