Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=31162976
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
TRPC6 regulates phenotypic switching of vascular smooth muscle cells through
plasma membrane potential-dependent coupling with PTEN
#MMPMID31162976
Numaga-Tomita T
; Shimauchi T
; Oda S
; Tanaka T
; Nishiyama K
; Nishimura A
; Birnbaumer L
; Mori Y
; Nishida M
FASEB J
2019[Sep]; 33
(9
): 9785-9796
PMID31162976
show ga
Vascular smooth muscle cells (VSMCs) play critical roles in the stability and
tonic regulation of vascular homeostasis. VSMCs can switch back and forth between
highly proliferative synthetic and fully differentiated contractile phenotypes in
response to changes in the vessel environment. Although abnormal phenotypic
switching of VSMCs is a hallmark of vascular disorders such as atherosclerosis
and restenosis after angioplasty, how control of VSMC phenotypic switching is
dysregulated in pathologic conditions remains obscure. We found that inhibition
of canonical transient receptor potential 6 (TRPC6) channels facilitated
contractile differentiation of VSMCs through plasma membrane hyperpolarization.
TRPC6-deficient VSMCs exhibited more polarized resting membrane potentials and
higher protein kinase B (Akt) activity than wild-type VSMCs in response to TGF-?1
stimulation. Ischemic stress elicited by oxygen-glucose deprivation suppressed
TGF-?1-induced hyperpolarization and VSMC differentiation, but this effect was
abolished by TRPC6 deletion. TRPC6-mediated Ca(2+) influx and depolarization
coordinately promoted the interaction of TRPC6 with lipid phosphatase and tensin
homolog deleted from chromosome 10 (PTEN), a negative regulator of Akt
activation. Given the marked up-regulation of TRPC6 observed in vascular
disorders, our findings suggest that attenuation of TRPC6 channel activity in
pathologic VSMCs could be a rational strategy to maintain vascular quality
control by fine-tuning of VSMC phenotypic switching.-Numaga-Tomita, T.,
Shimauchi, T., Oda, S., Tanaka, T., Nishiyama, K., Nishimura, A., Birnbaumer, L.,
Mori, Y., Nishida, M. TRPC6 regulates phenotypic switching of vascular smooth
muscle cells through plasma membrane potential-dependent coupling with PTEN.
free
free
free
