Year: 2011
Type: dissertation
Abstract: By using an shRNA approach to knock down the expression of the prostaglandin (PG)-F 2α receptor (FP-R), the role of PGF 2α in the process of phenotypic transformation of normal rat kidney (NRK) fibroblasts has been studied.Our data show that PGF 2α up-regulates Cox-2 expression both at the mRNA and protein level, indicating that activation of FP-R in NRK fibroblasts induces a positive feedback loop in the production PGF 2α .Knock down of FP-R expression fully impaired the ability of PGF 2α to induce a calcium response and subsequent depolarization in NRK cells.However, these cells could still undergo phenotypic transformation when treated with a combination of EGF and retinoic acid, but in contrast to the wild-type cells, this process was not accompanied by a membrane depolarization to -20 mV.Knock down of FP-R expression also impaired the spontaneous firing of calcium action potentials by density-arrested NRK cells.These data show that a membrane depolarization is not a prerequisite for the acquisition of a transformed phenotype.Furthermore, our data provide the first direct evidence that activity of PGF 2α by putative pacemaker cells underlies the generation of calcium action potentials in NRK monolayers.GF growth factor; RA, retinoic acid; TGFβ, transforming growth factor beta; FP-R, prostanoidThe abbreviations used are: [Ca 2+ ] i , intracellular Ca 2+ concentration; EGF, epidermal FP receptor; COX, cyclo-oxygenase; Ptfgr, gene encoding FP-R.
Author: W.H.M. Almirza
Language: English
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2144627694