Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28506310
&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
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28506310
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Skelet+Muscle
2017 ; 7
(1
): 7
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Unexpected evolutionarily conserved rapid effects of viral infection on oxytocin
receptor and TGF-?/pSmad3
#MMPMID28506310
Liu Y
; Conboy I
Skelet Muscle
2017[May]; 7
(1
): 7
PMID28506310
show ga
BACKGROUND: shRNA lentiviral vectors are extensively used for gene knockdowns in
mammalian cells, and non-target shRNAs typically are considered the proper
experimental control for general changes caused by RNAi. However, the effects of
non-target lentivirus controls on the modulation of cell signaling pathways
remain largely unknown. In this study, we evaluated the effect of control
lentiviral transduction on oxytocin receptor (OXTR) expression through the
ERK/MAPK pathway in mouse and human skeletal muscle cells, on myogenic activity,
and in vivo on mouse muscle regeneration. Furthermore, we mined published data
for the influence of viral infections on OXTR levels in human populations and
found that unrelated viral pathologies have a common consequence: diminished
levels of OXTR. METHODS: We examined the change in OXTR mRNA expression upon
transduction with control and Smad3-targeting viral vectors through real time
RT-PCR and Western blotting, and confirmed with immunofluorescence. Changes in
Smad3 and OXTR expression were examined both in vitro with mouse and human
myoblasts and in vivo in mouse satellite cells. The general effects of viral
infections on OXTR downregulation in humans were also examined by analyzing
published Gene Expression Omnibus (GEO) datasets. The change in myoblast myogenic
activity caused by the viral transduction (the percent of Pax7?+?Ki67+ cells) was
examined by immunofluorescence. RESULTS: Results shown in this work establish
that lentiviral control vectors significantly downregulate OXTR expression at
mRNA and protein levels and diminish key downstream effectors of OXTR, ERK
signaling, reducing the myogenic proliferation of infected cells. This effect is
evolutionarily conserved between mouse and human myogenic cells, and it manifests
in satellite cells after control lentiviral transduction of mice in vivo.
Furthermore, an examination of published datasets uncovered similar OXTR
downregulation in humans that are afflicted with different viral infections.
Additionally, cells transduced with Smad3-targeting shRNA downregulate OXTR even
more than cells transduced with control viruses. CONCLUSIONS: Our work suggests
that experimental cohorts transduced with control viruses may not behave the same
as un-transduced cells and animals, specifically that control viral vectors
significantly change the intensity of key cell-signaling pathways, such as
OXTR/ERK. Our results further demonstrate that lentiviral transduction
significantly decreases myogenic proliferation and suggest that viral infections
in general may play a role in decreasing muscle health and regeneration, a
decline in metabolic health, and a lower sense of well-being, as these rely on
effective OXTR signaling. Additionally, our data suggest pathway crosstalk
between TGF-?/pSmad3 and OXTR, implying that sustained attenuation of the
TGF-?/pSmad3 pathway will reduce pro-regenerative OXTR/pERK signaling.
free
free
free
