D Galli1, C Carubbi1, E Masselli2, D Corradi1, A Dei Cas2, A Nouvenne3, G Bucci1, M L Arcari1, P Mirandola1, M Vitale4, G Gobbi1. 1. Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy & Histology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy. 2. Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126 Parma, Italy. 3. Department of Clinical Sciences Sec. Internal Medicine and Critical Long-Term Care University Hospital, Via Gramsci 14, 43126 Parma, Italy. 4. Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy & Histology Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy. Electronic address: marco.vitale@unipr.it.
Abstract
RATIONALE: Vessel formation is a crucial event in tissue repair after injury. Thus, one assumption of innovative therapeutic approaches is the understanding of its molecular mechanisms. Notwithstanding our knowledge of the role of Protein Kinase C epsilon (PKCε) in cardio-protection and vascular restenosis, its role in vessel progenitor differentiation remains elusive. OBJECTIVE: Given the availability of PKCε pharmacological modulators already tested in clinical trials, the specific aim of this study is to unravel the role of PKCε in vessel progenitor differentiation, with implications in vascular pathology and vasculogenesis. METHODS AND RESULTS: Mouse Peri-Vascular Adipose Tissue (PVAT) was used as source of mesenchymal vessel progenitors. VEGF-induced differentiation of PVAT cells down-regulates both PKCε and p-PAK1 protein expression levels. PKCε overexpression and activation: i) reduced the expression levels of SMA and PECAM in endothelial differentiation of PVAT cells; ii) completely abrogated tubules formation in collagen gel assays; iii) increased the expression of p-PAK1. CONCLUSION: PKCε negatively interferes with vessel progenitor differentiation via interaction with PAK-1.
RATIONALE: Vessel formation is a crucial event in tissue repair after injury. Thus, one assumption of innovative therapeutic approaches is the understanding of its molecular mechanisms. Notwithstanding our knowledge of the role of Protein Kinase C epsilon (PKCε) in cardio-protection and vascular restenosis, its role in vessel progenitor differentiation remains elusive. OBJECTIVE: Given the availability of PKCε pharmacological modulators already tested in clinical trials, the specific aim of this study is to unravel the role of PKCε in vessel progenitor differentiation, with implications in vascular pathology and vasculogenesis. METHODS AND RESULTS:Mouse Peri-Vascular Adipose Tissue (PVAT) was used as source of mesenchymal vessel progenitors. VEGF-induced differentiation of PVAT cells down-regulates both PKCε and p-PAK1 protein expression levels. PKCε overexpression and activation: i) reduced the expression levels of SMA and PECAM in endothelial differentiation of PVAT cells; ii) completely abrogated tubules formation in collagen gel assays; iii) increased the expression of p-PAK1. CONCLUSION: PKCε negatively interferes with vessel progenitor differentiation via interaction with PAK-1.
Authors: D Di Marcantonio; D Galli; C Carubbi; G Gobbi; V Queirolo; S Martini; S Merighi; M Vaccarezza; N Maffulli; S M Sykes; M Vitale; P Mirandola Journal: Exp Cell Res Date: 2015-09-30 Impact factor: 3.905
Authors: Flavio L Ronzoni; Nefele Giarratana; Stefania Crippa; Mattia Quattrocelli; Marco Cassano; Gabriele Ceccarelli; Laura Benedetti; Jens Van Herck; Maria G Cusella De Angelis; Marco Vitale; Daniela Galli; Maurilio Sampaolesi Journal: Int J Mol Sci Date: 2021-02-16 Impact factor: 5.923