Our major interest is to understand the process­es of normal myogenesis and fibrosis associated to skeletal muscle diseases such as Duchenne Muscular Dystrophy. In particular, we are study­ing the role of the extracellular matrix (ECM), transforming growth factor ß (TGF-ß), connec­tive tissue growth factor (CTGF) and LRP in these processes. Normal myogenesis requires interac­tions with ECM elements, including proteogly­cans that act as co-receptors for growth factors such as TGF-ß and CTGF. We know that during myogenesis three proteoglycans that bind TGF-ß exert crucial influences on the signaling path­way of this growth factor and LRP-1, located on the cell surface, seems to be directly involved in this signaling process. Thus, we are charac­terizing the control of TGF-ß and CTGF signal­ing by proteoglycans and LRP-1. On the other hand, CTGF is a fibrotic factor involved in the synthesis of connective tissue and ECM. We have found that skeletal muscle committed myoblasts dedifferentiate on addition of CTGF. Therefore, studies that integrate the role of all these factors are expected to provide important basic infor­mation on the mechanisms that underlie normal and altered skeletal muscle formation. Because fibrosis is a pathogenic process for a variety of other diseases, our results could lead to design therapies and/or disclose target molecules able to interfere with fibrosis in general.

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