Lysophosphatidylcholine induces platelet-derived growth factor gene expression in a human mesangial cell line.
BACKGROUND
Oxidized low-density lipoprotein (oxLDL) has been considered important in the pathogenesis of progressive renal injury. Lysophosphatidylcholine (lysoPC) is a major phospholipid component of oxLDL. On the other hand, platelet-derived growth factor (PDGF) has also been implicated in proliferative disease of the kidney. This study investigated the difference in the potential of PC and lysoPC to induce DNA synthesis and PDGF gene expression in a human glomerular mesangial cell line (HMCL).


METHODS
DNA synthesis in HMCL was measured by [3H] thymidine incorporation. The mRNA expression levels of the PDGF A chain and B chain genes were measured using reverse transcription-polymerase chain reaction.


RESULTS
LysoPC treatment up-regulated the [3H] thymidine incorporation level in a dose-dependent fashion. The [3H] thymidine incorporation level in HMCL coincubated with lysoPC started to increase after 4 hours of treatment, peaked at 24 hours, and decreased thereafter. The level in HMCL incubated with 100 microM of lysoPC (palmitoyl or stearoyl) increased to 7- or 10-fold of the control at peak time, respectively. However, PC treatment did not increase [3H] thymidine incorporation in HMCL. PC treatment did not induce mRNA expression of either PDGF A or B chain genes. LysoPC did not induce PDGF A chain mRNA expression either. The only B chain mRNA expression was induced by lysoPC. The mRNA expression level in HMCL treated with 50 microM lysoPC for two hours increased to 1.6-fold that of the control.


CONCLUSIONS
LysoPC may induce DNA synthesis in a mesangial cell through the induction of PDGF BB as an autocrine and paracrine growth factor.
Tone
Y
Y
3rd Department of Internal Medicine, Wakayama Medical College, Japan.
Yukawa
S
S
Varghese
Z
Z
Moorhead
J F
JF
D002460:Cell Line; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D008244:Lysophosphatidylcholines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D014316:Tritium; D004247:DNA; D013936:Thymidine