Glomerular epithelial cells produce endothelin-1.

Abstract

Endothelin-1, a vasoactive peptide originally isolated from vascular endothelial cell culture supernatants, has constricting or mitogenic effects on smooth muscle and glomerular mesangial cells. Whether or not cultured rat glomerular epithelial cells synthesize endothelin-1 was assessed. Under basal culture conditions, the synthesis and release of endothelin-1 peptide by glomerular epithelial cells was time dependent, reaching 0.231 +/- 0.017 pg/1,000 cells at 24 h. For comparison, unstimulated bovine pulmonary artery endothelial cells and rat mesangial cells produced 0.982 +/- 0.237 and 0.004 +/- 0.002 pg of endothelin-1 peptide/1,000 cells per 24 h, respectively. In addition to endothelin-1 peptide, unstimulated glomerular epithelial cells expressed preproendothelin-1 mRNA. Transforming growth factor-beta, complement C5b-9, thrombin, and phorbol myristate acetate significantly enhanced endothelin-1 peptide synthesis in glomerular epithelial cells (45, 15, 55, and 25% above basal levels at 24 h, respectively), whereas epidermal growth factor had no effect. Thrombin and phorbol myristate acetate appeared to stimulate endothelin-1 peptide by activating protein kinase C, because the protein kinase inhibitor 1-(5-isoquinolinyl-sulfonyl)-3-methyl-piperazine abolished the thrombin- and phorbol myristate acetate-induced rise in endothelin-1 but had no effect on basal production. The stimulatory effect of thrombin was also markedly diminished in glomerular epithelial cells that had been depleted of protein kinase C by prolonged preincubation with a high dose of phorbol myristate acetate. Thus, glomerular epithelial cells may be an important source of endothelin-1, which might influence glomerular vasoconstriction or proliferation of target cells, particularly in the presence of proinflammatory molecules in the glomerulus.

Metabolic acidosis in chronic kidney disease: mere consequence or also culprit?

“…Another hormone that seems to be inflicted in MA-mediated kidney fibrosis is ET1, a peptide predominantly produced by the endothelium, though glomerular epithelial and mesangial cells also contribute to synthesis [ 25 , 32 , 120 ]. Beyond its well-known function as potent vasoconstrictor, ET1 underpins several renal functions to maintain homeostasis, including maintaining podocyte integrity and increasing proximal and distal tubular acidification in response to a dietary acid challenge [ 28 , 118 ].…”

Crosstalk mechanisms between glomerular endothelial cells and podocytes in renal diseases and kidney transplantation

“…In bovine ECs, interferon-gamma cotreatment potentiates the TNF-α effect by boosting ET-1 synthesis [ 38 ]. TGF-β can stimulate ET-l secretion in cultured MCs [ 39 ], endothelial [ 40 ], glomerular epithelial [ 41 ], as well as tubular epithelial cells (TECs) [ 42 ]. These results suggest that different cytokines and growth factors can regulate ET expression in the allograft during the immunological response to alloantigen stimuli.…”