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Journal of Lipid Research, Vol. 45, 1266-1271, July 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Association of hepatic lipase with proteoglycans stimulates the production of proteoglycans in vivo and in vitro

Sung-Joon Lee^1,, Sujata Kadambi^*, Christopher David^*, Allen D. Cooper^*, and Sungshin Y. Choi^2,*

^* Research Institute, Palo Alto Medical Foundation, 795 El Camino Real, Ames Building, Palo Alto, CA 94301
Stanford University, School of Medicine, Stanford, CA 94305

² To whom correspondence should be addressed. e-mail: chois{at}pamfri.org

HL is synthesized in hepatocytes and functions while bound to heparan sulfate proteoglycans (HSPGs) in sinusoidal endothelial cells. The HL-mediated uptake of lipoprotein requires cell-surface HSPG. The present study tested whether HL plays a role in the production of HSPG. The production of HSPG in Chinese hamster ovary (CHO) cells was determined by measuring the incorporation of ³⁵SO₄ into PGs. HL-producing HL-CHO cells showed approximately 30% more cellular PG than did wild-type (WT) cells. In contrast, PG production in cells producing a membrane-anchored HL-glycophosphatidylinositol (GPI) that was not bound to HSPG was virtually identical to that in WT cells. When purified HL was added to the WT- or HL-GPI cells, PG production increased significantly to a level similar to that of the HL-secreting cells, suggesting that the binding of HL to HSPG triggered the increased HSPG production. Heparin reduced PG production in HL-producing cells, confirming that PG production is stimulated only when HL is present as a ligand for HSPG. Real-time PCR and Northern blots demonstrated that PG production was significantly reduced in animals lacking HL.

Together, these data suggest that the binding of HL to PG on the cell surface exerts a positive feedback on cellular PG production.

Abbreviations: apo, apolipoprotein; CHO, Chinese hamster ovary; FGF, fibroblast growth factor; GAG, glycosaminoglycan; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GPI, glycophosphatidylinositol; HSPG, heparan sulfate proteoglycan; KO, knock-out; LRP, LDL receptor-related protein; McA, McArdle RH-7777; PG, proteoglycan; syn-1, syndecan-1; WT, wild-type

Supplementary key words heparin • cell culture • glycophosphatidylinositol • real-time polymerase chain reaction • hepatic lipase-deficient mice

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