TY - JOUR
T1 - Injury-elicited differential transcriptional regulation of phospholipid growth factor receptors in the cornea
AU - Wang, De An
AU - Du, Haiming
AU - Jaggar, Jonathan H.
AU - Brindley, David N.
AU - Tigyi, Gabor J.
AU - Watsky, Mitchell A.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - The phospholipid growth factors (PLGFs), including lysophosphatidic acid (LPA), have been implicated in corneal wound healing. PLGF concentrations and activities are elevated after corneal injury. Using real-time PCR, we quantified receptor mRNA levels in the healing rabbit cornea. In intact corneas, transcripts for S1P1, LPA1, and LPA3 receptor subtypes were detected, as was lipid phosphate phosphatase 1 (LPP1). After wounding, the trend for endothelium and keratocytes was for significant decreases in transcript numbers for the three receptor subtypes, whereas epithelial cells showed increased transcript numbers, except for an S1P1 decrease in healing cells. LPP1 transcript numbers were decreased in keratocytes and endothelium, although LPP-specific activity was unchanged. LPA-elicited Ca2+ transients were significantly reduced in the healing endothelium. Consistent with reduced LPA3 receptor numbers, dioctylglycerol pyrophosphate, a selective antagonist, reduced LPA-induced Ca2+ transients 2.7-fold in nonwounded epithelium but only 1.5-fold in wound-healing endothelium. These data for the first time establish physiologically relevant differential changes in the expression of PLGF receptor subtypes and provide evidence for the changing role of LPA3 receptors in endothelial cells.
AB - The phospholipid growth factors (PLGFs), including lysophosphatidic acid (LPA), have been implicated in corneal wound healing. PLGF concentrations and activities are elevated after corneal injury. Using real-time PCR, we quantified receptor mRNA levels in the healing rabbit cornea. In intact corneas, transcripts for S1P1, LPA1, and LPA3 receptor subtypes were detected, as was lipid phosphate phosphatase 1 (LPP1). After wounding, the trend for endothelium and keratocytes was for significant decreases in transcript numbers for the three receptor subtypes, whereas epithelial cells showed increased transcript numbers, except for an S1P1 decrease in healing cells. LPP1 transcript numbers were decreased in keratocytes and endothelium, although LPP-specific activity was unchanged. LPA-elicited Ca2+ transients were significantly reduced in the healing endothelium. Consistent with reduced LPA3 receptor numbers, dioctylglycerol pyrophosphate, a selective antagonist, reduced LPA-induced Ca2+ transients 2.7-fold in nonwounded epithelium but only 1.5-fold in wound-healing endothelium. These data for the first time establish physiologically relevant differential changes in the expression of PLGF receptor subtypes and provide evidence for the changing role of LPA3 receptors in endothelial cells.
KW - Calcium
KW - Diacylglycerol pyrophosphate
KW - Lysophosphatidic acid
KW - Phospholipid
KW - Wound healing
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U2 - 10.1152/ajpcell.00323.2002
DO - 10.1152/ajpcell.00323.2002
M3 - Article
C2 - 12388084
AN - SCOPUS:0036889313
SN - 0363-6143
VL - 283
SP - C1646-C1654
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 6 52-6
ER -