PMID- 26497118 OWN - NLM STAT- MEDLINE DCOM- 20161006 LR - 20171116 IS - 1098-1136 (Electronic) IS - 0894-1491 (Linking) VI - 64 IP - 3 DP - 2016 Mar TI - Fibroblast-derived tenascin-C promotes Schwann cell migration through beta1-integrin dependent pathway during peripheral nerve regeneration. PG - 374-85 LID - 10.1002/glia.22934 [doi] AB - Peripheral nerve regeneration requires precise coordination and dynamic interaction among various types of cells in the tissue. It remains unclear, however, whether the cellular crosstalk between fibroblasts and Schwann cells (SCs) is related to phenotype modulation of SCs, a critical cellular process after peripheral nerve injury. In this study, microarray analysis revealed that a total of 6,046 genes were differentially expressed in the proximal nerve segment after sciatic nerve transection in rats, and bioinformatics analysis further identified tenascin-C (TNC), an extracellular matrix (ECM) protein, as a key gene regulator. TNC was abundantly produced by nerve fibroblasts accumulating at the lesion site, rather than by SCs as usually expected. TNC significantly promoted SC migration without effects on SC proliferation in primary culture. In co-culture of fibroblasts and SCs, inhibition of TNC expression either by siRNA transfection or antibody blockade could suppress SC migration, while TNC-stimulated SC migration was mediated by TNC binding to beta1-integrin receptor in SCs through activation of Rac1 effectors. The in vivo evidence showed that exogenous TNC protein enhanced SC migration and axonal regrowth. Our results highlight that TNC-mediated cellular interaction between fibroblasts and SCs may regulate SC migration through beta1-integrin-dependent pathway during peripheral nerve regeneration. CI - (c) 2015 Wiley Periodicals, Inc. FAU - Zhang, Zhanhu AU - Zhang Z AD - Model Animal Research Center, Nanjing University, Nanjing, China. AD - Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. FAU - Yu, Bin AU - Yu B AD - Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. FAU - Gu, Yun AU - Gu Y AD - Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. FAU - Zhou, Songlin AU - Zhou S AD - Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. FAU - Qian, Tianmei AU - Qian T AD - Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. FAU - Wang, Yongjun AU - Wang Y AD - Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. FAU - Ding, Guohui AU - Ding G AD - Key Lab of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. FAU - Ding, Fei AU - Ding F AD - Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. FAU - Gu, Xiaosong AU - Gu X AD - Model Animal Research Center, Nanjing University, Nanjing, China. AD - Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151024 PL - United States TA - Glia JT - Glia JID - 8806785 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD68 antigen, human) RN - 0 (Integrin beta1) RN - 0 (S100 Calcium Binding Protein beta Subunit) RN - 0 (Tenascin) RN - EC 1.14.11.2 (Procollagen-Proline Dioxygenase) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) RN - EC 5.3.4.1 (P4hb protein, rat) RN - EC 5.3.4.1 (Protein Disulfide-Isomerases) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - Antigens, Differentiation, Myelomonocytic/metabolism MH - Cell Movement/*drug effects MH - Cell Proliferation/drug effects/genetics MH - Cells, Cultured MH - Coculture Techniques MH - Disease Models, Animal MH - Fibroblasts/physiology MH - Gene Regulatory Networks MH - Integrin beta1/*metabolism MH - Male MH - Nerve Regeneration/*physiology MH - Procollagen-Proline Dioxygenase/metabolism MH - Protein Disulfide-Isomerases/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - S100 Calcium Binding Protein beta Subunit/metabolism MH - Schwann Cells/*drug effects MH - Sciatic Neuropathy/*pathology/physiopathology MH - Signal Transduction/*drug effects/genetics/physiology MH - Tenascin/metabolism/*pharmacology MH - Time Factors MH - Wound Healing/drug effects/genetics MH - rho GTP-Binding Proteins/metabolism OTO - NOTNLM OT - Schwann cells OT - cell migration OT - crosstalk OT - fibroblasts OT - sciatic nerve injury OT - tenascin-C EDAT- 2015/10/27 06:00 MHDA- 2016/10/08 06:00 CRDT- 2015/10/27 06:00 PHST- 2014/10/14 00:00 [received] PHST- 2015/09/28 00:00 [accepted] PHST- 2015/10/27 06:00 [entrez] PHST- 2015/10/27 06:00 [pubmed] PHST- 2016/10/08 06:00 [medline] AID - 10.1002/glia.22934 [doi] PST - ppublish SO - Glia. 2016 Mar;64(3):374-85. doi: 10.1002/glia.22934. Epub 2015 Oct 24.