Basement Membrane Thickening and Extracellular Matrix Expansion

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Thickening of capillary basement membrane is one of the early structural abnormalities observed in almost all the tissues, including the vascular system in diabetes (151). Because basement membrane can affect numerous cellular functions, such as in structure support, vascular permeability, cell adhesion, proliferation, differentiation, and gene expression, alterations in its components may cause vascular dysfunctions.

Histologically, increases in type IV and VI collagen, fibronectin and laminin and decreases in proteoglycans are observed in the mesangium of diabetic patients with nephropathy and probably in the vascular endothelium in general (152,153). These effects can be replicated in mesangial cells incubated in increasing glucose levels that were prevented general PKC inhibitors (154-156). Additionally, increased expression of transforming growth factor (TGF)- P has been implicated in the development of mesangial expansion and basement membrane thickening in diabetes. Because PKC activation can increase the production of ECM and TGF-P, it is not surprising that several reports have shown that PKC inhibitors can also prevent hyperglycemia- or diabetes-induced increases in ECM and TGF-P in mesangial cells or renal glomeruli (98).

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