Cardiac fibroblast-myofibroblast transformation (CMT) is a critical event in the initiation of myocardial fibrosis. Notch signaling has been shown to regulate myofibroblast transformation from other kinds of cells. However, whether Notch signaling is also involved in CMT remains unclear. In the present study, expressions of Notch receptors in cardiac fibroblasts (CFs) were examined, effects of Notch signaling inhibitor N-[N-(3,5-difluorophenacetyl)- l-alanyl]-S-phenylglycine t-butyl ester (DAPT) and transforming growth factor-β1 (TGF-β1) on CMT were determined by increasing alpha-smooth muscle actin (α-SMA) expression and collagen synthesis, and Notch signaling was examined by analyzing expressions of Notch receptors. The results showed that: (1) Notch receptor 1, 2, 3 and 4 were all expressed in CFs; (2) DAPT promoted CMT in a time-dependent manner; (3) During the period of CMT induced by TGF-β1, expressions of Notch receptor 1, 3 and 4 in CFs were down-regulated, whereas there was no change for Notch receptor 2. Moreover, the downtrends of Notch 1, 3 and 4 were corresponding to the trend growth of α-SMA expression and collagen synthesis. These results suggested that inhibiting of Notch signaling might promote CMT. The down-regulations of Notch receptor 1, 3 and 4 induced by TGF-β1 may facilitate CMT. In conclusion, inhibition of Notch signaling might be a novel mechanism of CMT in myocardial fibrosis.
- MeSH
- buněčná diferenciace MeSH
- down regulace MeSH
- fibroblasty cytologie metabolismus MeSH
- kardiomyocyty cytologie metabolismus MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- myofibroblasty cytologie metabolismus MeSH
- novorozená zvířata MeSH
- potkani Sprague-Dawley MeSH
- receptory Notch metabolismus MeSH
- signální transdukce fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
The aim of this study was to determine the effect and mechanism of low concentration of lidocaine on subthreshold membrane potential oscillations (SMPO) and burst discharges in chronically compressed dorsal root ganglion (DRG) neurons. DRG neurons were isolated by enzymatic dissociation method. SMPO, burst discharges and single spike were elicited by whole cell patchclamp technique in current clamp mode. Persistent Na+ current (INaP) and transient Na+ current (INaT) were elicited in voltage clamp mode. The results showed that SMPO was suppressed and burst discharges were eliminated by tetrodotoxin (TTX, 0.2 µmol/l) in current clamp mode, INaP was blocked by 0.2 µmol/l TTX in voltage clamp mode. SMPO, burst discharges and INaP were also suppressed by low concentration of lidocaine (10 µmol/l) respectively. However, single spike and INaT could only be blocked by high concentration of lidocaine (5 mmol/l). From these results, it is suggested that INaP mediates the generation of SMPO in injured DRG neurons. Low concentration of lidocaine (10 µmol/l) suppresses SMPO by selectively inhibiting INaP, but not INaT, in chronically compressed DRG neurons.
- Klíčová slova
- Lidocaine, Neuropathic pain, Dorsal root ganglion, Ectopic discharges, Subthreshold membrane potential oscillations, Persistent Na+ current,
- MeSH
- anestetika lokální farmakologie MeSH
- blokátory sodíkových kanálů MeSH
- elektrofyziologie MeSH
- financování organizované MeSH
- interpretace statistických dat MeSH
- krysa rodu rattus MeSH
- lidokain farmakologie MeSH
- membránové potenciály účinky léků MeSH
- metoda terčíkového zámku MeSH
- neurony metabolismus účinky léků MeSH
- potkani Sprague-Dawley MeSH
- sodíkové kanály metabolismus účinky léků MeSH
- spinální ganglia cytologie metabolismus účinky léků MeSH
- tetrodotoxin farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
