Fibroblast-derived tenascin-C promotes Schwann cell migration through β1-integrin dependent pathway during peripheral nerve regeneration.
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 β1-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 β1-integrin-dependent pathway during peripheral nerve regeneration.
Model Animal Research Center, Nanjing University, Nanjing, China.|Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Zhanhu
Z
Zhang
Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Bin
B
Yu
Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Yun
Y
Gu
Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Songlin
S
Zhou
Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Tianmei
T
Qian
Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Yongjun
Y
Wang
Key Lab of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Guohui
G
Ding
Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Fei
F
Ding
Model Animal Research Center, Nanjing University, Nanjing, China.|Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Xiaosong
X
Gu
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000502:physiology; D053263:Gene Regulatory Networks; D019012:Integrin beta1 / Q000378:metabolism*; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects*; D020426:Sciatic Neuropathy / Q000473:pathology* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019063:Tenascin / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019012:Integrin beta1; D011393:Procollagen-Proline Dioxygenase; D019704:Protein Disulfide-Isomerases; D064568:S100 Calcium Binding Protein beta Subunit; D019063:Tenascin; D020741:rho GTP-Binding Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C526501:P4hb protein, rat
Schwann cells; cell migration; crosstalk; fibroblasts; sciatic nerve injury; tenascin-C