title: Spatiotemporal expression of KHSRP modulates Schwann cells and neuronal differentiation after sciatic nerve injury.
abstract: K-homology splicing regulator protein (KHSRP), a multifunctional RNA-binding protein, was originally thought to primarily control mRNA decay. KHSRP was shown to be involved in p38MAPK, NF-κB and the JAK2-STAT-1a pathways. Besides, KHSRP regulated neuronal localization of beta-actin and microtubule-associated protein 2 (MAP2) mRNAs, respectively. However, the expression and roles of KHSRP in peripheral system lesions and repair are still unknown. In our study, we found that KHSRP levels were relatively higher in the crushed sciatic nerves, significantly reached a highest level at day 5. Spatially, we observed that KHSRP had a major colocalization with Schwann cells (SCs) and neurons. KHSRP was connected with promyelinating SCs marker. KHSRP promoted the decay of beta-catenin (β-catenin) mRNA which was inactivated by PI3K-AKT signaling. We doubted that KHSRP might participate in Schwann cells differentiation by regulation of β-catenin mRNA decay. In vitro, in cyclic adenosine monophosphate (cAMP)-induced Schwann cells differentiation system, we detected the increased KHSRP in cytoplasm and decreased β-catenin at protein and mRNA level. In differentiation model of rat pheochromocytoma cells (PC12) induced by nerve growth factor (NGF) and primary dorsal root ganglion (DRG) cell culture, KHSRP also acted on neuronal differentiation. Specially, KHSRP-specific siRNA-transfected cells did not show morphological change, which was similar to β-catenin overexpressed SCs. During SC/neuron co-cultures, KHSRP was transported to cytoplasm and involved in SCs myelination. In conclusion, we speculated that KHSRP was involved in SCs and neuronal differentiation by inducing β-catenin mRNA decay.
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China; Department of Orthopaedics, Affiliated Mental Health Center of Nantong University, Nantong 226001, People's Republic of China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Immunology, Medical College, Nantong University, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Immunology, Medical College, Nantong University, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Immunology, Medical College, Nantong University, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Immunology, Medical College, Nantong University, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Aisong
authors.initials: A
authors.lastname: Guo
authors.affiliation: Department of Immunology, Medical College, Nantong University, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China. Electronic address: luncky0513@126.com.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D000242:Cyclic AMP
keywords: Differentiation; KHSRP; Neuron; Schwann cells; Sciatic nerve injury; β-catenin