PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway
| العنوان: | PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway |
|---|---|
| المؤلفون: | Johan Lennartsson, Tijs van Wieringen, Lars Rask, Vahid Reyhani, Kristofer Rubin, Maria Tsioumpekou |
| المصدر: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| بيانات النشر: | Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Contraction (grammar), Science, Becaplermin, Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy), macromolecular substances, Biology, Models, Biological, environment and public health, Article, 03 medical and health sciences, chemistry.chemical_compound, Phosphatidylinositol 3-Kinases, Growth factor receptor, Humans, Phosphatidylinositol, Phosphorylation, Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci), Protein kinase C, Actin, Protein Kinase C, Multidisciplinary, 030102 biochemistry & molecular biology, Phospholipase C gamma, Cofilin, Fibroblasts, Cell biology, 030104 developmental biology, chemistry, Biochemistry, Actin Depolymerizing Factors, Gene Knockdown Techniques, biology.protein, Medicine, Collagen, Signal transduction, Gels, Platelet-derived growth factor receptor, Signal Transduction |
| الوصف: | Cell-mediated contraction of collagenous matrices is modulated by various growth factors and cytokines, such as platelet-derived growth factor-BB (PDGF-BB). Here we used a genetic cell model to delineate defined signaling pathways that enhance collagen gel contraction downstream of ligand-stimulated platelet-derived growth factor receptor-β (PDGF-Rβ). Our data show that PDGF BB-enhanced activations of phosphatidylinositol 3′-kinase (PI3K) and phospholipase Cγ (PLCγ) were necessary for PDGF-enhanced collagen gel contraction. Importantly, other defined signaling pathways down-stream of PDGF-Rβ were, however, dispensable. The decisive roles for PI3K and PLCγ were corroborated by experiments using selective inhibitors. Furthermore, we show that de-phosphorylation and thereby activation of cofilin that is important for the turnover of actin filaments, is depended on PI3K and PLCγ down-stream of PDGF-Rβ. Moreover, inhibition of protein kinase C (PKC) by GÖ6976 and bisindolylmaleimide-II abolished cofilin de-phosphorylation, as well as PDGF-enhanced contraction. In contrast, activation of the PKC protein family by 4β-phorbol 12-myristate 13-acetate (PMA) did not accelerate collagen gel contraction although it induced long-term cofilin de-phosphorylation, showing the need of a dynamic control of cofilin de-phosphorylation for PDGF-enhanced collagen gel contraction. Taken together, our data point to the involvement of a PI3K/PLCγ-PKC-cofilin pathway in both PDGF-enhanced cofilin de-phosphorylation and PDGF-enhanced collagen gel contraction. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f7b6526cbf3f8b0ec07406ec0f64814 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-331647 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8f7b6526cbf3f8b0ec07406ec0f64814 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |