[Human proximal tubular epithelial cells activated by low density lipoprotein promote phenotypic changes in renal interstitial fibroblasts].
OBJECTIVE
To study the effects of low density lipoprotein (LDL) on human proximal tubular epithelial cells (HK-2), and further examine the effects of HK-2 activated by LDL on phenotypic changes in human renal interstitial fibroblasts (RIFB).


METHODS
3H-thymidine incorporation and direct cell counting were performed to detect cell proliferation. Message RNA and protein of alpha-smooth muscle-actin (alpha-SM-actin) were analyzed by Northern and Western blot. Fibronectin or laminin levels were determined using an inhibition enzyme linked immunosorbant assay. After exposed to LDL-activated HK-2 conditioned media (CM), total collagen synthesis or collagen III mRNA expression was measured by proline incorporation or RT-PCR in primary cultures of RIFB.


RESULTS
Incubation of HK-2 with LDL (100-500 micrograms/ml) for 72 hours stimulated HK-2 proliferation. mRNA expression, protein synthesis of alpha-SM-actin and secretory fibronectin level were up-regulated by LDL at a concentration of 250 micrograms/ml. When exposed to CM from LDL-treated HK-2, thymidine incorporation rate was not changed in RIFB, but alpha-SM-actin production was significantly enhanced. CM from LDL-treated HK-2 also showed the stimulated proline incorporation and secretion of fibronectin or laminin. Expression collegen III mRNA was up-regulated by CM from LDL-treated HK-2 cells.


CONCLUSIONS
The results indicate that LDL stimulates HK-2 cells proliferation, phenotypic changes and fibronectin synthesis. Human proximal tubular epithelial cells activated by LDL modulate the phenotype and matrix production in RIFB.
Li
J
J
Institute of Nephrology, Renal Division, Department of Medicine, The First Teaching Hospital, Beijing Medical University, Beijing 100034, China.
Li
X
X
Wang
H
H
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000494:pharmacology*
D008077:Lipoproteins, LDL