@article{PurbaBrunkenPeakeetal.2017,
  author    = {Purba, Talveen S. and Brunken, Lars and Peake, Michael and Shahmalak, Asim and Chaves, Asuncion and Poblet, Enrique and Ceballos, Laura and Gandarillas, Alberto and Pausa, Ralf},
  title     = {Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: Lessons from the human hair follicle matrix},
  series = {European journal of cell biology},
  volume    = {96},
  journal   = {European journal of cell biology},
  publisher = {Elsevier},
  address   = {Jena},
  issn      = {0171-9335},
  doi       = {10.1016/j.ejcb.2017.03.011},
  pages     = {632 -- 641},
  year      = {2017},
  abstract  = {Human hair follicle (HF) growth and hair shaft formation require terminal differentiation-associated cell cycle arrest of highly proliferative matrix keratinocytes. However, the regulation of this complex event remains unknown. CIP/KIP family member proteins (p21(CIP1), p27(KIP1) and p57(KIP2)) regulate cell cycle progression/arrest, endoreplication, differentiation and apoptosis. Since they have not yet been adequately characterized in the human HF, we asked whether and where CIP/KIP proteins localise in the human hair matrix and pre-cortex in relation to cell cycle activity and HF-specific epithelial cell differentiation that is marked by keratin 85 (K85) protein expression. K85 expression coincided with loss or reduction in cell cycle activity markers, including in situ DNA synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1, affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of CIP/KIP proteins was found abundantly within the proliferative hair matrix, concomitant with a role in cell cycle checkpoint control. p21(CIP1), p27(Klp1) and cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas p57(MP2) protein decreased but became nuclear. These data imply a supportive role for CIP/KIP proteins in maintaining proliferative arrest, differentiation and anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft formation in anagen VI. Moreover, post-mitotic hair matrix regions contained cells with enlarged nuclei, and DNA in situ hybridisation showed cells that w ere >2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance cyclin E to control further rounds o f DNA replication in a cell population that has a propensity to become tetraploid. These data shed new light on the in situ-biography of human hair matrix keratinocytes on their path of active cell cycling, arrest and terminal differentiation, and showcase the human HF as an excellent, clinically relevant model system for cell cycle physiology research of human epithelial cells within their natural tissue habitat. Crown Copyright (C) 2017 Published by Elsevier GmbH. All rights reserved.},
  language  = {en}
}
@article{BoehmFloesserErmleretal.2013,
  author    = {B{\"o}hm, Andreas and Fl{\"o}ßer, Anja and Ermler, Swen and Fender, Anke C. and L{\"u}th, Anja and Kleuser, Burkhard and Schr{\"o}r, Karsten and Rauch, Bernhard H.},
  title     = {Factor-Xa-induced mitogenesis and migration require sphingosine kinase activity and S1P formation in human vascular smooth muscle cells},
  series = {Cardiovascular research},
  volume    = {99},
  journal   = {Cardiovascular research},
  number    = {3},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0008-6363},
  doi       = {10.1093/cvr/cvt112},
  pages     = {505 -- 513},
  year      = {2013},
  abstract  = {Sphingosine-1-phosphate (S1P) is a cellular signalling lipid generated by sphingosine kinase-1 (SPHK1). The aim of the study was to investigate whether the activated coagulation factor-X (FXa) regulates SPHK1 transcription and the formation of S1P and subsequent mitogenesis and migration of human vascular smooth muscle cells (SMC). FXa induced a time- (36 h) and concentration-dependent (330 nmol/L) increase of SPHK1 mRNA and protein expression in human aortic SMC, resulting in an increased synthesis of S1P. FXa-stimulated transcription of SPHK1 was mediated by the protease-activated receptor-1 (PAR-1) and PAR-2. In human carotid artery plaques, expression of SPHK1 was observed at SMC-rich sites and was co-localized with intraplaque FX/FXa content. FXa-induced SPHK1 transcription was attenuated by inhibitors of Rho kinase (Y27632) and by protein kinase C (PKC) isoforms (GF109203X). In addition, FXa rapidly induced the activation of the small GTPase Rho A. Inhibition of signalling pathways which regulate SPHK1 expression, inhibition of its activity or siRNA-mediated SPHK1 knockdown attenuated the mitogenic and chemotactic response of human SMC to FXa. These data suggest that FXa induces SPHK1 expression and increases S1P formation independent of thrombin and that this involves the activation of Rho A and PKC signalling. In addition to its key function in coagulation, this direct effect of FXa on human SMC may increase cell proliferation and migration at sites of vessel injury and thereby contribute to the progression of vascular lesions.},
  language  = {en}
}