The glomerular mesangial cell: an expanding role for a specialized pericyte

The mesangial cell occupies a central position in the renal glomerulus. It has characteristics of a modified smooth muscle cell, but is also capable of a number of other functions. Among these are generation of prostaglandins (PGs) and mediators of inflammation; production and breakdown of basement membrane and other biomatrix material; synthesis of cytokines; and uptake of macromolecules, including immune complexes. In terms of its smooth muscle activity, the mesangial cell contracts or relaxes in response to a number of vasoactive agents. This ability allows the cells to modify glomerular filtration locally. The cellular mechanism of action of many agents influencing mesangial cells involves activation of phospholipase C for phosphatidylinositol 4,5-bisphosphate. This results in generation of inositol trisphosphate and release of intracellular calcium. Mesangial cell relaxation can be mediated by enhanced cAMP or cGMP generation. Many vasoactive substances also stimulate PG production by mesangial cells. This involves activation of both phospholipase C and A2, the latter being responsible for the release of arachidonic acid. Mesangial cells are also capable of endocytosis of macromolecules, including immune complexes. This is initiated by binding to a specific receptor, resulting in formation of PG, platelet-activating factor, and reactive oxygen species. Mesangial cells can generate interleukin 1 and platelet-derived growth factor and respond to these in an autocrine manner. Thus, the mesangial cell not only can control glomerular filtration, but may also be involved in the response to local injury, including cell proliferation and basement membrane remodeling.