Lysophosphatidic acid-induced calcium mobilization and proliferation in kidney proximal tubular cells

Dixon, Richard J., Ken Young, and Nigel J. Brunskill. Lysophosphatidic acid-induced calcium mobilization and proliferation in kidney proximal tubular cells. Am. J. Physiol. 276 (Renal Physiol. 45): F191-F198, 1999. -Patients with proteinuria tend to develop progressive renal disease with proximal tubular cell atrophy and interstitial scarring. It has been suggested that the nephrotoxicity of albuminuric states may be due to the protein molecule itself or by lipids, such as lysophosphatidic acid (LPA), that albumin carries. LPA was found to cause a transient increase in intracytoplasmic free Ca(2+) ([Ca(2+)](i)) in opossum kidney proximal tubule cells (OK) that was maximal at 100 mu M LPA and was dose dependent with an EC(50) of 2.6 x 10(-6) M. This Ca(2+) mobilization was from both internal stores and across the plasma membrane and was pertussis toxin (PTX) insensitive. Treatment of OK cells with 100 mu M LPA for 5 min was found to cause a twofold increase in [(3)H]thymidine incorporation and a three- to fivefold increase over control after 24 h. This was highly PTX sensitive and insensitive to pretreatment with the tyrosine kinase inhibitors genistein and herbimycin A. These findings may be of significance in the progression of renal disease and indicate the potential importance of lipids in modulating proximal tubule cell function and growth.