کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1964055 | 1058524 | 2008 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Role of the prostanoid FP receptor in action potential generation and phenotypic transformation of NRK fibroblasts Role of the prostanoid FP receptor in action potential generation and phenotypic transformation of NRK fibroblasts](/preview/png/1964055.png)
By using an shRNA approach to knockdown the expression of the prostaglandin (PG)-F2α receptor (FP-R), the role of PGF2α in the process of phenotypic transformation of normal rat kidney (NRK) fibroblasts has been studied. Our data show that PGF2α 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 PGF2α. Knockdown of FP-R expression fully impaired the ability of PGF2α 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. Knockdown 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 PGF2α by putative pacemaker cells underlies the generation of calcium action potentials in NRK monolayers.
Journal: Cellular Signalling - Volume 20, Issue 11, November 2008, Pages 2022–2029