AIMS: Abnormal production of lysophosphatidic acid (LPA), an important lysophospholipid mediator, in the kidney was examined to participate in the pathogenesis of renal fibrosis in rats. The secretory lysophospholipase D activity of autotoxin was considered as a possible pathway for extracellular production of LPA in the pathological renal fluids. MAIN METHODS: In this study of rats with unilateral ureteral obstruction for two weeks, we measured concentrations of LPA and its precursor, lysophosphatidylcholine stored in the urinary bladder and present in the swollen pelvis of the ligated kidney as well as the corresponding blood plasma by liquid chromatography-tandem mass spectrometry. KEY FINDINGS: We found that concentrations of LPA and lysophosphatidylcholine accumulated in the effluent in the swollen pelvis of the ligated kidney of unilateral ureteral obstruction rats were much higher than those in the urinary bladder. The molecular species composition of LPA in the former was considerably different from that in the blood plasma, indicating the involvement of an additional source other than the blood circulation supplying LPA to the effluent in the swollen kidney. A potential mechanism is increased release of LPA from activated renal cells in the ureter-ligated kidney. SIGNIFICANCE: Both pathways for supply of extracellular LPA may participate in the induction and progression of renal tubulofibrosis.
AIMS: Abnormal production of lysophosphatidic acid (LPA), an important lysophospholipid mediator, in the kidney was examined to participate in the pathogenesis of renal fibrosis in rats. The secretory lysophospholipase D activity of autotoxin was considered as a possible pathway for extracellular production of LPA in the pathological renal fluids. MAIN METHODS: In this study of rats with unilateral ureteral obstruction for two weeks, we measured concentrations of LPA and its precursor, lysophosphatidylcholine stored in the urinary bladder and present in the swollen pelvis of the ligated kidney as well as the corresponding blood plasma by liquid chromatography-tandem mass spectrometry. KEY FINDINGS: We found that concentrations of LPA and lysophosphatidylcholine accumulated in the effluent in the swollen pelvis of the ligated kidney of unilateral ureteral obstructionrats were much higher than those in the urinary bladder. The molecular species composition of LPA in the former was considerably different from that in the blood plasma, indicating the involvement of an additional source other than the blood circulation supplying LPA to the effluent in the swollen kidney. A potential mechanism is increased release of LPA from activated renal cells in the ureter-ligated kidney. SIGNIFICANCE: Both pathways for supply of extracellular LPA may participate in the induction and progression of renal tubulofibrosis.
Authors: Norihiko Sakai; Jerold Chun; Jeremy S Duffield; David Lagares; Takashi Wada; Andrew D Luster; Andrew M Tager Journal: Kidney Int Date: 2016-12-04 Impact factor: 10.612