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Paricalcitol Inhibits Aldosterone-Induced Proinflammatory Factors by Modulating
Epidermal Growth Factor Receptor Pathway in Cultured Tubular Epithelial Cells
#MMPMID26064952
Morgado-Pascual JL
; Rayego-Mateos S
; Valdivielso JM
; Ortiz A
; Egido J
; Ruiz-Ortega M
Biomed Res Int
2015[]; 2015
(?): 783538
PMID26064952
show ga
Chronic kidney disease is characterized by Vitamin D deficiency and activation of
the renin-angiotensin-aldosterone system. Increasing data show that vitamin D
receptor agonists (VDRAs) exert beneficial effects in renal disease and possess
anti-inflammatory properties, but the underlying mechanism remains unknown.
Emerging evidence suggests that "a disintegrin and metalloproteinase"
(ADAM)/epidermal growth factor receptor (EGFR) signalling axis contributes to
renal damage. Aldosterone induces EGFR transactivation regulating several
processes including cell proliferation and fibrosis. However, data on tubular
epithelial cells is scarce. We have found that, in cultured tubular epithelial
cells, aldosterone induced EGFR transactivation via TGF-?/ADAM17. Blockade of the
TGF-?/ADAM17/EGFR pathway inhibited aldosterone-induced proinflammatory gene
upregulation. Moreover, among the potential downstream mechanisms, we found that
TGF-?/ADAM17/EGFR inhibition blocked ERK and STAT-1 activation in response to
aldosterone. Next, we investigated the involvement of TGF-?/ADAM17/EGFR axis in
VDRA anti-inflammatory effects. Preincubation with the VDRA paricalcitol
inhibited aldosterone-induced EGFR transactivation, TGF-?/ADAM-17 gene
upregulation, and downstream mechanisms, including proinflammatory factors
overexpression. In conclusion, our data suggest that the anti-inflammatory
actions of paricalcitol in tubular cells could depend on the inhibition of
TGF-?/ADAM17/EGFR pathway in response to aldosterone, showing an important
mechanism of VDRAs action.
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