Lysophosphatidic acid and mesangial cells: implications for renal diseases

The last decade has witnessed a phenomenal increase in our understanding of the biological role of lysophosphatidic acid (LPA) and has led to an appre ciation of this critical serum-derived growth factor released from platelet s. We herein summarize recent observations that collectively support the hy pothesis that LPA may play a key role in the pathogenesis of initiation and progression of proliferative glomerulonephritis. LPA synergistically stimu lates mesangial cell proliferation in combination with platelet-derived gro wth factor in primary culture. The mechanism of co-mitogenesis is likely to be mediated by the prolonged activation of mitogen-activated protein kinas e which is stimulated by platelet-derived growth factor and LPA through dif ferent mechanisms. LPA contracts cultured mesangial cells and has propertie s in common with other presser molecules including mobilization of intracel lular Ca2+ and promotion of Ca2+ entry through dihydropyridine-sensitive ca lcium channels. LPA receptor mRNA has been identified in isolated glomeruli dissected from renal biopsy samples of patients with IgA nephropathy. All of these facts have led us to postulate that LPA is produced within glomeru li and that LPA's mitogenic as well as haemodynamic action contribute to th e pathological process of mesangial proliferative glomerulonephritis. The p ossible production of LPA as an autocrine factor from mesangial cells thems elves has also been discussed.