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  • br Conclusion In conclusion the number of endogenous residen

    2018-11-12


    Conclusion In conclusion, the number of endogenous resident c-Kit+Lin− CSCs increased during physiological cardiac hypertrophy, whereas neither Sca-1+Lin− CSCs nor cardiac muscle-derived stromal Bisindolylmaleimide V seemed to contribute to the physiological cardiac remodeling that results from swimming exercise training in mice. The following are the supplementary data related to this article.
    Acknowledgements The authors would like to thank CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), an agency of the Brazilian government, for PhD fellowships to Camila Ferreira Leite, Carolina Salomão Lopes, Marilia Beatriz Cuba, Angélica Cristina Alves, Caroline Santos Capitelli Fuzaro, Lidiane Pereira Garcia and Marcos Vinícius da Silva, and for a financial support grant (PNPD/CAPES-2011-2016) to Valdo José Dias da Silva. The authors also would like to thank CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for financial support grants (no. 309521/2013-0 and no. 467129/2014-2) to Valdo José Dias da Silva.
    Introduction Maintenance and repair of most epithelia are achieved by stem cells, which must undergo cell division in order to self-renew and must also be capable of cell division, resulting in daughter cells that migrate and differentiate into multiple lineages of the particular epithelium (Barker et al., 2010; Blanpain et al., 2007; Potten and Loeffler, 1990). The pancreatic epithelium is thought to have a low turnover rate under normal physiologic conditions (Grapin-Botton, 2005; Bonner-Weir and Sharma, 2002); however, it is capable of rapid regeneration in response to inflammatory injury (Finegood et al., 1995; Neuschwander-Tetri et al., 2000). The existence of somatic stem cells and their contribution to pancreatic epithelial renewal and regeneration after injury are poorly understood. Perhaps some of the best studied models of epithelial regeneration from a somatic stem cell niche are in the GI system (Koo and Clevers, 2014; Español-Suñer et al., 2012; Williams et al., 2014; Barker, 2014). The liver has a low rate of cellular turnover but high regenerative potential. Its parenchyma relies initially on a mechanism of self-duplication, and relies on stem cells, ductular oval cells, only when hepatocyte division is inhibited. In the intestinal system, the epithelial turnover occurs every 3–5days, while Paneth cells are supplied every 3–6weeks. Epithelial stem cells exist in a protected microenvironment called niches. These niches contain several different cell types initially defined by their proliferative properties: the label retaining cell (LRC), likely the true stem cell, which normally has a lower rate of division but can transform into a proliferative and multipotential stem cell during injury; and the transient amplifying (TA) cell which is believed to be a direct progeny of the true stem cell and are capable of division but for a restricted period of time (Blanpain et al., 2007; Hoffmann, 2008). Despite the extensive characterization of these stem cell niches in the colon and small intestine, only a few molecular markers for these cells have been identified. Several studies strongly implicate Lgr5 and Lrig1 as markers and regulators of the stem cell compartment (Barker et al., 2012). Epithelial regeneration and renewal from progenitor niches throughout the gastrointestinal system require a complex balance of proliferation, migration and differentiation. As newly generated cells migrate from the stem cell compartment, they differentiate to acquire the phenotype of their terminally differentiated lineages. This migration is regulated, in part, by the Trefoil Factor Family (TFF) of proteins. There are three members within this family TFF-1, TFF-2 and TFF-3. All TFFs are protease resistant proteins, which are best known for their important roles in epithelial repair after inflammatory injury (Hoffmann, 2005; Taupin and Podolsky, 2003). The TFFs are abundantly secreted onto the mucosal surface by mucus-secreting cells of the gastrointestinal tract and the pancreatic duct (Ebert et al., 1999; Madsen et al., 2007). In the stomach the expression of TFF-1 and -2 is rapidly up-regulated at the margin of mucosal injury, and their fundamental function is to promote epithelial repair by cell migration.