Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 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\26375954
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2015 ; 10
(9
): e0138425
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Transforming Growth Factor Beta (TGF-?) Is a Muscle Biomarker of Disease
Progression in ALS and Correlates with Smad Expression
#MMPMID26375954
Si Y
; Kim S
; Cui X
; Zheng L
; Oh SJ
; Anderson T
; AlSharabati M
; Kazamel M
; Volpicelli-Daley L
; Bamman MM
; Yu S
; King PH
PLoS One
2015[]; 10
(9
): e0138425
PMID26375954
show ga
We recently identified Smads1, 5 and 8 as muscle biomarkers in human ALS. In the
ALS mouse, these markers are elevated and track disease progression. Smads are
signal transducers and become activated upon receptor engagement of ligands from
the TGF-? superfamily. Here, we sought to characterize ligands linked to
activation of Smads in ALS muscle and their role as biomarkers of disease
progression. RNA sequencing data of ALS muscle samples were mined for TGF-?
superfamily ligands. Candidate targets were validated by qRT-PCR in a large
cohort of human ALS muscle biopsy samples and in the G93A SOD1 mouse. Protein
expression was evaluated by Western blot, ELISA and immunohistochemistry. C2C12
muscle cells were used to assess Smad activation and induction. TGF-?1, 2 and 3
mRNAs were increased in ALS muscle samples compared to controls and correlated
with muscle strength and Smads1, 2, 5 and 8. In the G93A SOD1 mouse, the temporal
pattern of TGF-? expression paralleled the Smads and increased with disease
progression. TGF-?1 immunoreactivity was detected in mononuclear cells
surrounding muscle fibers in ALS samples. In muscle cells, TGF-? ligands were
capable of activating Smads. In conclusion, TGF-?1, 2 and 3 are novel biomarkers
of ALS in skeletal muscle. Their correlation with weakness in human ALS and their
progressive increase with advancing disease in the ALS mouse suggest that they,
as with the Smads, can track disease progression. These ligands are capable of
upregulating and activating Smads and thus may contribute to the Smad signaling
pathway in ALS muscle.