Gender differences characterize amyotrophic lateral sclerosis (ALS). Since ALS patients have increased circulating levels of transforming growth factor beta 1 (TGFB1), here we analysed gender and disease progression related modification of TGFB1 and its related signaling molecules in spinal cord and skeletal muscle of ALS mice and in muscle biopsies from sporadic ALS patients. At presymptomatic (PS) stage Tgfb1 expression is reduced in mouse spinal cord, but is increased selectively in male skeletal muscle. At symptomatic (S) stage Tgfb1 is induced both in mouse spinal cord and muscle, as well as in muscle of ALS patients. Tgfbr2 levels are induced only in mouse spinal cord. Smad2 and Smad4 are decreased in mouse spinal cord and muscle, but SMAD2 protein levels are augmented selectively in male mouse muscle. Smad3 mRNA and SMAD3 protein are increased in mouse muscle. Genes controlled by TGFB1 in muscle (Pax7, Collagen1a1 and Fibronectin) are reduced both in male and female ALS mice at S stage. Thus, TGFB1 modulation may serve as a novel therapeutic target for ALS.
Transforming Growth Factor beta 1 signaling is altered in the spinal cord and muscle of amyotrophic lateral sclerosis mice and patients / M. Meroni, V. Crippa, R.M. Cristofani, P. Rusmini, M.E. Cicardi, E. Messi, M. Piccolella, B. Tedesco, V. Ferrari, G. Sorarù, M. Pennuto, A. Poletti, M. Galbiati. - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - 82(2019 Oct), pp. 48-59. [10.1016/j.neurobiolaging.2019.07.001]
Transforming Growth Factor beta 1 signaling is altered in the spinal cord and muscle of amyotrophic lateral sclerosis mice and patients
M. Meroni;V. Crippa;R.M. Cristofani;P. Rusmini;M.E. Cicardi;E. Messi;M. Piccolella;B. Tedesco;V. Ferrari;A. Poletti
;M. Galbiati
2019
Abstract
Gender differences characterize amyotrophic lateral sclerosis (ALS). Since ALS patients have increased circulating levels of transforming growth factor beta 1 (TGFB1), here we analysed gender and disease progression related modification of TGFB1 and its related signaling molecules in spinal cord and skeletal muscle of ALS mice and in muscle biopsies from sporadic ALS patients. At presymptomatic (PS) stage Tgfb1 expression is reduced in mouse spinal cord, but is increased selectively in male skeletal muscle. At symptomatic (S) stage Tgfb1 is induced both in mouse spinal cord and muscle, as well as in muscle of ALS patients. Tgfbr2 levels are induced only in mouse spinal cord. Smad2 and Smad4 are decreased in mouse spinal cord and muscle, but SMAD2 protein levels are augmented selectively in male mouse muscle. Smad3 mRNA and SMAD3 protein are increased in mouse muscle. Genes controlled by TGFB1 in muscle (Pax7, Collagen1a1 and Fibronectin) are reduced both in male and female ALS mice at S stage. Thus, TGFB1 modulation may serve as a novel therapeutic target for ALS.File | Dimensione | Formato | |
---|---|---|---|
Accepted PDF.pdf
Open Access dal 01/11/2020
Descrizione: Accepted manuscript
Tipologia:
Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione
1.59 MB
Formato
Adobe PDF
|
1.59 MB | Adobe PDF | Visualizza/Apri |
1-s2.0-S0197458019301964-main.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
1.53 MB
Formato
Adobe PDF
|
1.53 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.