TRPC1 channels regulate the activation of pancreatic stellate cells through ERK1/2 and SMAD2 pathways and perpetuate their pressure-mediated activation
| العنوان: | TRPC1 channels regulate the activation of pancreatic stellate cells through ERK1/2 and SMAD2 pathways and perpetuate their pressure-mediated activation |
|---|---|
| المؤلفون: | Silviya, Radoslavova, Benedikt, Fels, Zoltan, Pethö, Matthias, Gruner, Tobias, Ruck, Sven G, Meuth, Antoine, Folcher, Natalia, Prevarskaya, Albrecht, Schwab, Halima, Ouadid-Ahidouch |
| المساهمون: | Laboratoire de Physiologie Cellulaire et Moléculaire - UR UPJV 4667 (LPCM), Université de Picardie Jules Verne (UPJV), Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la physiopathologie de la prostate, Université de Lille, Sciences et Technologies-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital Düsseldorf, Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Westfälische Wilhelms-Universität Münster = University of Münster (WWU) |
| المصدر: | Cell Calcium Cell Calcium, 2022, 106, pp.102621. ⟨10.1016/j.ceca.2022.102621⟩ |
| بيانات النشر: | Elsevier BV, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Pancreatic stellate cells, High-pressure, MAP Kinase Signaling System, Physiology, Activation, Smad2 Protein, Cell Biology, Pancreatic Neoplasms, Pancreatic ductal adenocarcinoma, Mice, TRPC1 channels, Tumor Microenvironment, Animals, Humans, Extracellular Signal-Regulated MAP Kinases, Molecular Biology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Carcinoma, Pancreatic Ductal, TRPC Cation Channels |
| الوصف: | International audience; Pancreatic stellate cell (PSC) activation is a major event occurring during pancreatic ductal adenocarcinoma (PDAC) development. Up to now mechanisms underlying their activation by mechanical cues such as the elevated tissue pressure in PDAC remain poorly understood. Here we investigate the role of one potential mechano-transducer, TRPC1 ion channel, in PSC activation. Using pre-activated human siTRPC1 and murine TRPC1-KO PSCs, we show that TRPC1 promotes αSMA (α-smooth muscle actin) expression, the main activation marker, in cooperation with the phosphorylated SMAD2, under normal and elevated pressure. Functional studies following TRPC1 silencing demonstrate the dual role of TRPC1 in the modulation of PSC proliferation and IL-6 secretion through the activation of ERK1/2 and SMAD2 pathways. Moreover, pressurization changes the mechanical behavior of PSCs by increasing their cellular stiffness and emitted traction forces in a TRPC1-dependent manner. In summary, these results point to a role of TRPC1 channels in sensing and transducing the characteristic mechanical properties of the PDAC microenvironment in PSCs. |
| تدمد: | 0143-4160 1532-1991 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d374992f3ec686cd5bb1f2307b9b786aTest https://doi.org/10.1016/j.ceca.2022.102621Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....d374992f3ec686cd5bb1f2307b9b786a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01434160 15321991 |
|---|