Eicosanoid-induced growth and signaling events in rat glomerular mesangial cells. Prostaglandins 1995 May;49(5):269-83
Date
05/01/1995Pubmed ID
7659782DOI
10.1016/0090-6980(95)00049-gScopus ID
2-s2.0-0029018043 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
Renal glomerular injury frequently results in proliferation of a specialized supporting cell of the glomerular capillary known as the mesangial cell. In various forms of renal injury there is enhanced glomerular synthesis of specific eicosanoids of the arachidonic cyclooxygenase and lipoxygenase pathways including prostaglandin (PG) F2 alpha, thromboxane (Tx) A2, the hydroxyeicosatetraenoic acids 12-HETE and 5-HETE, and the leukotrienes LTB4 and LTD4 and attempts have been made to link these eicosanoids with injury-induced mesangial cell growth. In this study, the growth promoting effect of these eicosanoids on glomerular mesangial cells was correlated with activation of two growth regulatory enzymes: phospholipase C (PLC) and protein kinase C (PKC). PGF2 alpha, and TxA2 endoperoxide analog U-46619, and LTD4 significantly enhanced DNA synthesis [(as assessed by [3H]thymidine (TdR) incorporation)] in relatively quiescent (0.5% serum) mesangial cells, activated PLC [as assessed by increased 1,4,5-inositol tris-phosphate (IP3) generation and diacylglycerol (DAG) synthesis], and activated PKC (as assessed by translocation of the enzyme activity from the cytosol to the membrane). The effect of PGF2 alpha on IP3 generation was not blocked by the TxA2 receptor antagonist, SQ-29,548. PGF2 alpha was the most effective eicosanoid in inducing all three events, and concentrations that enhanced TdR incorporation (1 microM) also activated PLC and PKC. In contrast, concentrations of U-46619 and LTD4 which enhanced TdR incorporation (1 microM), also activated PLC, but were insufficient to also activate PKC. Our observations indicate that the growth-promoting effect of PGF2 alpha, U-46619, and LTD4 can best be correlated with PLC activation. In addition, PGF2 alpha does not mediate PLC activation through binding to the TxA2 receptor.
Author List
Kelefiotis D, Bresnahan BA, Stratidakis I, Lianos EAAuthor
Barbara A. Bresnahan MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Animals
Cell Division
DNA
Diglycerides
Dinoprost
Eicosanoids
Enzyme Activation
Glomerular Mesangium
Hydroxyeicosatetraenoic Acids
Leukotriene B4
Leukotriene D4
Prostaglandin Endoperoxides, Synthetic
Protein Kinase C
Rats
Rats, Sprague-Dawley
Receptors, Thromboxane
Signal Transduction
Thromboxane A2
Type C Phospholipases
