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Direct Effects of VEGF and VEGF Receptor Inhibitor on Proliferation of Human Renal Proximal Tubular Epithelial Cells (HRPTEC)
Author(s) -
Gu JianWei,
Shparago Megan,
Tan Wei,
Bailey Amelia Purser
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a764-a
Subject(s) - autocrine signalling , paracrine signalling , endocrinology , medicine , cell growth , receptor , umbilical vein , vascular endothelial growth factor , vegf receptors , chemistry , cancer research , in vitro , biochemistry
Clinical models link VEGF inhibition to hypertension. However, the role of VEGF in renal mechanisms of hypertension is poorly understood. We seek to determine if VEGF or VEGF receptor inhibitor (SU5416) directly affects proliferation of cultured HRPTEC, compared to human umbilical vein endothelial cells (HUVEC), and human aortic smooth muscle cells (HASMC). 3H‐thymidine incorporation was determined in those cells following exposure to VEGF (10 ng/ml), VEGF plus SU5416 (10 μmol/L), SU5416 (1, 5, 10, & 20 μmol/L), vehicle control for 18 hrs. VEGF slightly but significantly increased proliferation of HRPTEC, compared to the control (10%, P=0.012, n=6). There was a significant decrease in proliferation of HRPTEC treated with VEGF plus SU5416, compared to the control (65%, P<0.001). VEGF caused a 2‐fold increase in proliferation of HUVEC, compared to the control (P<0.001), but its action was completely abolished by SU5416. Neither VEGF nor SU5416 exerted any effect on proliferation of cultured HASMC. In addition, SU5416 caused a dose‐related inhibition in proliferation of HRPTEC, but 20 μmol/L of SU5416 did not further blunt proliferation of HRPTEC. We first reported that VEGF receptor blocker inhibited proliferation of HRPTEC, and demonstrated that VEGF signaling system plays a major role in proliferation of HRPTEC though other signaling systems may be involved in regulating the proliferation. These findings also suggest autocrine and paracrine functions of VEGF on HRPTEC. Together, the results support the hypothesis that VEGF may play an important role in renal mechanisms of hypertension. (NHI/AA013821‐01A2; NIH/HL51971).