Human renal fibroblasts derived from normal and fibrotic kidneys show differences in increase of extracellular matrix synthesis and cell proliferation upon angiotensin II exposure

Abstract

Angiotensin II (Ang II) as a vasoactive hormone may be involved in progressive renal interstitial fibrosis. We investigated the influence of Ang II on cell proliferation and synthesis of extracellular matrix (collagen I, III and fibronectin) in human renal fibroblasts derived from normal (TK 173 cell line) and fibrotic (TK 188 cell line) kidneys which possess both Ang II type l and type 2 (AT1 and AT2) receptors. Incubation of the cells with Ang II increased the cell proliferation and the synthesis of extracellular matrix significantly in both cell lines. However, proliferation and extracellular matrix synthesis showed a greater increase in the cells derived from the fibrotic kidney. The Ang II mediated effect on cell proliferation and extracellular matrix synthesis was diminished in the presence of the AT1 receptor blocker losartan in both cell lines. No inhibition was observed using the AT2 receptor blocker PD123319. Ang II induced cell proliferation could be completely inhibited by incubation with human TGF-beta1 antibody. Incubation with Ang II did not affect TGF beta 1 production but in untreated cells TGF-beta 1 content was higher in the cells derived from the fibrotic kidney. This might be the reason for the more sensitive reaction on exposure to Ang II.

Effect of combination therapy with enalapril and the TGF-β antagonist 1D11 in unilateral ureteral obstruction

“…ANG II-induced stimulation of collagen IV synthesis in tubular cells (34) and ANG II-induced ECM production in glomerular cells are both mediated by TGF-␤ (5). Similar effects have been noted with fibroblasts and vascular smooth muscle cells (26,28). In the present experiments, we combined a TGF-␤ antibody 1D11 with enalapril, an ACE inhibitor.…”

Development and Preliminary Validation of Non-Governmental Organization Practice Checklist

“…The internal consistency shows the relationship among the items of a questionnaire (15,16,18). Reliability coefficient of 0.70 or more for a tool is acceptable to be used in a study (26), but alpha coefficient should not be more than 0.90 because this shows repetitive items (27). Our checklist alpha coefficient was 0.70, and the checklist showed to be reliable for use in our study.…”

Profibrotic Phenotype of Conjunctival Fibroblasts from Mucous Membrane Pemphigoid

“…Profibrotic phenotypes are observed and maintained in vitro in fibroblasts from patients with scleroderma, pulmonary, renal, and colonic fibrosis. [13][14][15] There is some evidence of phenotypic changes in fibroblasts isolated from mucous membrane pemphigoid patients, 16 -18 but whether there are pathological alterations in key aspects of fibroblast behavior, such as motility, contractile function, matrix synthesis, and development of myofibroblast characteristics, has not been investigated. Moreover, whether there are differences in fibroblasts isolated from actively inflamed tissue compared with fibroblasts isolated from clinically uninflamed tissue is unknown.…”