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Regulation of IGF and PDGF receptors in the skeletal muscle of mice with Neuraminidase-1 deficiency

Grant number: 14/02501-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2014
Effective date (End): April 30, 2018
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Edmar Zanoteli
Grantee:Juliana de Carvalho Neves
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


The neuraminidase-1 (Neu1) regulates the catabolism of sialoglycoconjugates in lysosomes. Congenital deficiency of Neu1 is the basis of sialidosis, a severe neurosomatic disease associated with osteoskeletal deformities, hypotonia and muscle weakness. Neu1 deficient mice (Neu1-/-) develop an atypical form of muscular degeneration characterized by expansion of extracellular matrix (ECM), invasion of muscle fibers by fibroblasts, cytoplasmic fragmentation, vacuolization and muscle atrophy. The excessive proliferation of fibroblasts suggests that Neu1 is related to the control of cellular proliferative capacity. The increased gelatinolytic activity observed in the ECM occur in order to degrade accumulated components, such as collagen, and it is believed to be the major mechanism responsible for facilitation of migration and invasion by fibroblasts. Fibroblasts from patients with sialidosis present high proliferative capacity, possibly due to increased response to PDGF-BB and IGF-2. In arterial smooth muscle cells, Neu1 would desialylate PDGF and IGF receptors and thus reduce proliferation in these cells. Furthermore, an inverse relation between the expression of Neu1 and malignancy of cancer cells is reported. The aims of this study are to investigate the expression of membrane receptors involved in cell proliferation pathways such as IGFr and PDGFr, which may act on fibroblasts proliferation in the skeletal muscle of Neu1-/- mice; evaluate drugs that inhibit the growth factor pathways involved; and determine whether these drugs reduce the changes in the ECM of these animals. The results obtained may bring important information about muscular involvement of Neu1 in the control of cell proliferation receptors, and in the physiopathogenesis of the muscular phenotypic alterations in Neu1 deficiency. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
NEVES, Juliana de Carvalho. Regulation of IGF and PDGF receptors in the skeletal muscle of neuraminidase 1 deficient mice. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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