title: Phosphatidylcholine-specific phospholipase C/heat shock protein 70 (Hsp70)/transcription factor B-cell translocation gene 2 signaling in rat bone marrow stromal cell differentiation to cholinergic neuron-like cells.
abstract: Although bone marrow stromal cells (BMSCs) can differentiate into neuron-like cells, the mechanisms underlying neuronal differentiation are not well understood. We recently found that inhibition of phosphatidylcholine-specific phospholipase C (PC-PLC) by its inhibitor D609 promoted BMSCs' differentiation into cholinergic neuron-like cells. Using the effective small molecule D609 and gene microarray technology, we investigated the change of gene expression profile to identify key mediators involved in the neuronal differentiation. We selected heat shock protein 70 (Hsp70) and transcription factor B-cell translocation gene 2 (Btg2) that were maximally up-regulated for further study. We found that functional suppression of Hsp70 blocked D609-induced increase of Btg2 expression and cholinergic neuronal differentiation of BMSCs. These results demonstrated that Hsp70 was the pivotal factor in PC-PLC-medicated neuronal differentiation of BMSCs, and Btg2 might be its downstream target. Our findings provide new clues for controlling BMSCs' differentiation into cholinergic neuron-like cells and provide a putative strategy for neurodegenerative diseases therapies.
authors.affiliation: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.forename: Chunhui
authors.initials: C
authors.lastname: Sun
authors.forename: Le
authors.initials: L
authors.lastname: Su
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Shangli
authors.initials: S
authors.lastname: Zhang
authors.forename: Junying
authors.initials: J
authors.lastname: Miao
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D059329:Cholinergic Neurons / Q000378:metabolism*; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D009636:Norbornanes; D020411:Oligonucleotide Array Sequence Analysis; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D059467:Transcriptome / Q000187:drug effects; D017855:Transferases (Other Substituted Phosphate Groups) / Q000037:antagonists & inhibitors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C521959:BTG2 protein, rat; D001559:Benzhydryl Compounds; D001952:Bridged-Ring Compounds; D018840:HSP70 Heat-Shock Proteins; D017874:Immediate-Early Proteins; C410027:KNK 437; D009636:Norbornanes; D011760:Pyrrolidinones; D013859:Thiocarbamates; D013871:Thiones; D025521:Tumor Suppressor Proteins; C046498:tricyclodecane-9-yl-xanthogenate; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C