Elevated hydrostatic pressure disturbs expression of growth factors in human renal epithelial cells

TL;DR

Elevated hydrostatic pressure changes the shape of kidney cells and disrupts the expression of growth factors, offering new insights into kidney injury from obstructive uropathy.

Contribution

This study reveals how prolonged hydrostatic pressure affects growth factor expression in human renal epithelial cells.

Findings

8-hour HP treatment increased TGFB1 and VEGFA but decreased CSF2 and TGFB2 expression.

48-hour HP treatment downregulated CSF2, TGFB2, PDGFB, VEGFA, and VEGFB, while upregulating TGFB3.

Changes from 48-hour HP treatment were more severe than those from 8-hour HP treatment.

Abstract

Obstructive uropathy is a common kidney disease caused by elevated hydrostatic pressure (HP), but relevant molecular and cellular mechanisms have not yet been well understood. In this study, we ex vivo investigated the effects of elevated HP on human renal epithelial cells (HREpCs). Primary HREpCs were subjected to 100 cmH2O HP for 8 or 48 h. Then, the cells were cultured without HP stimulation for another 24 h or 72 h. Cell morphology showed almost no change after 8h HP treatment, but exhibited reversible elongation after 48h HP treatment. HP treatment for 8 h increased the expression of TGFB1 and VEGFA but decreased the expression of CSF2 and TGFB2. On the other hand, HP treatment for 48 h downregulated the expression of CSF2, TGFB2, PDGFB, VEGFA, and VEGFB, while upregulated the expression of TGFB3. Interestingly, all changes induced by 48 h HP treatment were detected more severe compared to 8 h HP treatment. In conclusion, elongated ex vivo HP loading to renal epithelial cells induces reversible changes on cell morphology and disturbs the expression of several growth factors, which provides novel mechanistic insight on elevated HP-caused kidney injury such as obstructive uropathy.

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