[Changes in the organization of the extracellular matrix at the skin level during diabetes]

The ultrastructural study of cutaneous biopsies in diabetic patients highlighted in different phases of disease a progressive alteration of extracellular matrix (E.M.). In the initial phase of disease the morphologic aspect showed an increased accumulation of proteoglycan biglycan, laminin, fibronectin and type IV collagen. These components are responsible for the lamina lucida expansion and are induced by TGF-beta. In the last phase of the disease, an accumulation and a defective organization of E.M. component arises. Type V collagen, normally not present in the skin, is observed. In patients with over ten years of diabetic history, the morphological aspect is defined by a progressive disorganization of E.M. The formation of a vicious circle is responsible for the progressive remodeling of E.M. This process may be linked to the not enzymatic glycosylation of E.M., due to several episodes of hyperglycemia, and to autoinductive mechanisms of TGF-beta. These mechanisms are responsible for the cytokine synthesis and for the E.M. inhibition of degradation.