title: IL-22 Impedes the Proliferation of Schwann cells: Transcriptome Sequencing and Bioinformatics Analysis.
abstract: Schwann cells (SCs) proliferation is crucial for nerve regeneration following nerve injury. This study aims to investigate effects of interleukin-22 (IL-22) on SCs proliferation in vitro, as well as the corresponding mechanism. Rat SCs were treated with 100 ng/ml rat IL-22 for 48 h, and cell proliferation and apoptosis were detected using fluorescent staining and flow cytometry. After transcriptome sequencing, raw reads were filtered and mapped to reference genome rn5. Then, differentially expressed genes (DEGs) and long non-coding RNAs (DElncRNAs) between IL-22 and control groups were identified (tool: Cuffdiff). Functional and pathway enrichment analyses were performed (tool: GOFunction), and protein-protein interaction (PPI) network was constructed (tool: STRING and Cytoscape). Furthermore, Pearson's correlations between DEGs and DElncRNAs were analyzed, and regulatory network of DEGs, DElncRNAs, and transcription factors (TFs) was constructed. IL-22 significantly inhibited proliferation (p value < 0.05) and promoted apoptosis of Schwann cells. Totally, 932 DEGs and 118 DElncRNAs were identified, among which Ccl2 and Ccna2 were hub genes in PPI network. Up-regulated DEGs were enriched in apoptosis related terms, whereas down-regulated DEGs were enriched in proliferation related terms. DElncRNAs like NONRATT023505, NONRATG020400, and NONRATT022748 were correlated with multiple DEGs enriched in cell cycle and division. Moreover, up-regulated TFs Egr1, Cebpd, and Atf4 play crucial roles in regulatory network, and NONRATG020400-Cebpd-Ccl2, NONRATT023505/NONRATT022748-Atf4-Ccna2, and NONRATT022748-Egr1-Id1/Aldoc/Eno2/F3/Serpine1 regulatory pathways were identified in SCs after IL-22 treatment. IL-22 might influence SCs proliferation and apoptosis via regulating lncRNA-TF-gene pathways in SCs. However, more studies are required to confirm these results.
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Shengming
authors.initials: S
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200032, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Ao
authors.affiliation: Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Haihui
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Depeng
authors.initials: D
authors.lastname: Meng
authors.affiliation: Med-X Research Insitute of Shanghai Jiao Tong University, Shanghai, 200030, China. LishanWangfh@163.com.
authors.forename: Lishan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. lciryuan@163.com.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000187:drug effects; D007378:Interleukins / Q000494:pharmacology*; D060066:Protein Interaction Maps / Q000187:drug effects; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D062085:RNA, Long Noncoding; D014157:Transcription Factors; D000097043:Interleukin-22
keywords: Differentially expressed genes; Long non-coding RNA; Peripheral nerve injury; Schwann cell; Transcriptome sequencing