Transforming growth factor beta 1 signaling is altered in the spinal cord and muscle of amyotrophic lateral sclerosis mice and patients.

Transforming growth factor beta 1 signaling is altered in the spinal cord and muscle of amyotrophic lateral sclerosis mice and patients. Neurobiol Aging. 2019 Jul 10;82:48-59 Authors: Meroni M, Crippa V, Cristofani R, Rusmini P, Cicardi ME, Messi E, Piccolella M, Tedesco B, Ferrari V, Sorarù G, Pennuto M, Poletti A, Galbiati M Abstract Gender differences characterize amyotrophic lateral sclerosis (ALS). Because ALS patients have increased circulating levels of transforming growth factor beta 1 (TGFB1), here we analyzed gender and disease progression-related modification of TGFB1 and its related signaling molecules in the spinal cord and skeletal muscle of ALS mice and in muscle biopsies from sporadic ALS patients. At presymptomatic stage, Tgfb1 mRNA expression is reduced in the mouse spinal cord but is increased selectively in the male skeletal muscle. At symptomatic stage, it is induced both in the mouse spinal cord and muscle, as well as in the muscle of ALS patients. Tgfbr2 levels are induced only in the mouse spinal cord. Smad2 and Smad4 mRNAs are decreased in the mouse spinal cord and muscle, but SMAD2 protein levels are augmented selectively in the male mouse muscle. Smad3 mRNA and SMAD3 protein are increased in the mouse muscle. The expression of genes controlled by TGFB1 in the muscle (Pax7, Collagen1a1, and Fibronectin) are reduced both in male and female ALS mice at symptomatic stage. Thus, TGFB1 modulation may serve as a ...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research