Use this URL to cite or link to this record in EThOS:
Title: The role of basement membrane remodelling and laminin-111 in the adult skeletal muscle myogenesis
Author: Ranaldi, Daniele
ISNI:       0000 0004 8504 7691
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2019
Availability of Full Text:
Access from EThOS:
Access from Institution:
Satellite cells are skeletal muscle-specific stem cells that are responsible for the homeostasis and repair of the skeletal muscle tissue. Usually quiescent, satellite cells can be activated, enter the cell cycle, and differentiate to regenerate damaged muscle fibres. Satellite cells are positioned in a specific anatomical compartment between the basement membrane surrounding the myofibre and the myofibre sarcolemma. This location, known as the "niche" plays a central role in the regulation of stem cell activity. However, the relationship between the basal lamina and satellite cells has not been extensively examined. I hypothesized that the basal lamina, and in particular Laminins, has a key role in the control of satellite cells and adult myogenesis. Here, I report that the basement membrane undergoes a remodelling process to incorporate Laminin-111 upon activation of satellite cells. I showed that remodelling of the satellite cell basal lamina is mediated by Matrix Metalloproteinase 2 and 9, whose expression is up-regulated in activated satellite cells. Furthermore, I have examined the requirement for Laminin-111 in satellite cell-mediated muscle repair using pharmacological and genetics approaches. The outcome of my investigations reveals that Laminin-111 plays an essential role at different stages of adult myogenesis. Laminin-111 stimulates the activation of satellite cells and promotes their proliferation. Furthermore, Laminin-111 is required for self-renewal and long-term capacity to regenerate muscles following injury. These effects are dependent on the expression and function of Integrin α6, a receptor with high affinity for Laminin-111 normally down-regulated in adult muscle cells. These data provide novel insight into the mechanisms that control satellite cell activity, in particular their self-renewal, and offer a possible explanation for the known therapeutic effect of Laminin-111 treatments in animal models of congenital muscular dystrophies.
Supervisor: Borycki, A. G. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available