PMID- 31390799
OWN - NLM
STAT- MEDLINE
DCOM- 20200511
LR  - 20200511
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 8
IP  - 8
DP  - 2019 Aug 6
TI  - EGFR/ErbB Inhibition Promotes OPC Maturation up to Axon Engagement by 
      Co-Regulating PIP2 and MBP.
LID - 10.3390/cells8080844 [doi]
LID - 844
AB  - Remyelination in the adult brain relies on the reactivation of the Neuronal 
      Precursor Cell (NPC) niche and differentiation into Oligodendrocyte Precursor 
      Cells (OPCs) as well as on OPC maturation into myelinating oligodendrocytes 
      (OLs). These two distinct phases in OL development are defined by transcriptional 
      and morphological changes. How this differentiation program is controlled remains 
      unclear. We used two drugs that stimulate myelin basic protein (MBP) expression 
      (Clobetasol and Gefitinib) alone or combined with epidermal growth factor 
      receptor (EGFR) or Retinoid X Receptor gamma (RXRgamma) gene silencing to decode the 
      receptor signaling required for OPC differentiation in myelinating OLs. 
      Electrospun polystyrene (PS) microfibers were used as synthetic axons to study 
      drug efficacy on fiber engagement. We show that EGFR inhibition per se stimulates 
      MBP expression and increases Clobetasol efficacy in OPC differentiation. 
      Consistent with this, Clobetasol and Gefitinib co-treatment, by co-regulating 
      RXRgamma, MBP and phosphatidylinositol 4,5-bisphosphate (PIP2) levels, maximizes 
      synthetic axon engagement. Conversely, RXRgamma gene silencing reduces the ability of 
      the drugs to promote MBP expression. This work provides a view of how EGFR/ErbB 
      inhibition controls OPC differentiation and indicates the combination of 
      Clobetasol and Gefitinib as a potent remyelination-enhancing treatment.
FAU - Nocita, Emanuela
AU  - Nocita E
AD  - NeurotechIT Laboratory, Department of Biology, University of Rome "Tor Vergata", 
      00133 Rome, Italy.
FAU - Del Giovane, Alice
AU  - Del Giovane A
AD  - NeurotechIT Laboratory, Department of Biology, University of Rome "Tor Vergata", 
      00133 Rome, Italy.
FAU - Tiberi, Marta
AU  - Tiberi M
AD  - NeurotechIT Laboratory, Department of Biology, University of Rome "Tor Vergata", 
      00133 Rome, Italy.
FAU - Boccuni, Laura
AU  - Boccuni L
AD  - NeurotechIT Laboratory, Department of Biology, University of Rome "Tor Vergata", 
      00133 Rome, Italy.
FAU - Fiorelli, Denise
AU  - Fiorelli D
AD  - NeurotechIT Laboratory, Department of Biology, University of Rome "Tor Vergata", 
      00133 Rome, Italy.
FAU - Sposato, Carola
AU  - Sposato C
AD  - NeurotechIT Laboratory, Department of Biology, University of Rome "Tor Vergata", 
      00133 Rome, Italy.
FAU - Romano, Elena
AU  - Romano E
AD  - Advanced Microscopy Center, Department of Biology, University of Rome "Tor 
      Vergata", 00133 Rome, Italy.
FAU - Basoli, Francesco
AU  - Basoli F
AD  - Department of Engineering, Universita Campus Bio-Medico di Roma, 00128 Rome, 
      Italy.
FAU - Trombetta, Marcella
AU  - Trombetta M
AD  - Department of Engineering, Universita Campus Bio-Medico di Roma, 00128 Rome, 
      Italy.
FAU - Rainer, Alberto
AU  - Rainer A
AD  - Department of Engineering, Universita Campus Bio-Medico di Roma, 00128 Rome, 
      Italy.
FAU - Traversa, Enrico
AU  - Traversa E
AD  - School of Materials and Energy, University of Electronic Science and Technology 
      of China, Chengdu 611731, China.
FAU - Ragnini-Wilson, Antonella
AU  - Ragnini-Wilson A
AUID- ORCID: 0000-0001-7963-7554
AD  - NeurotechIT Laboratory, Department of Biology, University of Rome "Tor Vergata", 
      00133 Rome, Italy. antonella.ragnini@uniroma2.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190806
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Mbp protein, mouse)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Retinoid X Receptor gamma)
RN  - ADN79D536H (Clobetasol)
RN  - EC 2.7.10.1 (EGFR protein, mouse)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Line
MH  - Clobetasol/*pharmacology
MH  - ErbB Receptors/*metabolism
MH  - Gefitinib/*pharmacology
MH  - Myelin Basic Protein/*metabolism
MH  - *Oligodendrocyte Precursor Cells/cytology/metabolism
MH  - *Oligodendroglia/cytology/metabolism
MH  - Remyelination
MH  - Retinoid X Receptor gamma/*metabolism
PMC - PMC6721729
OTO - NOTNLM
OT  - EGFR inhibitor
OT  - drug screening
OT  - microfibers
OT  - remyelination
OT  - smoothened agonist
COIS- The authors declare no conflict of interest.
EDAT- 2019/08/09 06:00
MHDA- 2020/05/12 06:00
PMCR- 2019/08/01
CRDT- 2019/08/09 06:00
PHST- 2019/06/05 00:00 [received]
PHST- 2019/08/04 00:00 [revised]
PHST- 2019/08/05 00:00 [accepted]
PHST- 2019/08/09 06:00 [entrez]
PHST- 2019/08/09 06:00 [pubmed]
PHST- 2020/05/12 06:00 [medline]
PHST- 2019/08/01 00:00 [pmc-release]
AID - cells8080844 [pii]
AID - cells-08-00844 [pii]
AID - 10.3390/cells8080844 [doi]
PST - epublish
SO  - Cells. 2019 Aug 6;8(8):844. doi: 10.3390/cells8080844.