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Non-apoptotic role for caspase-7 in hair follicles and the surrounding tissue

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Abstract

Hair follicles are unique organs undergoing regular cycles of proliferation, differentiation, and apoptosis. The final step of apoptosis is, in general, mediated by executioner caspases comprising caspase-3, -6 and -7. Despite their commonly accepted apoptotic function, executioner caspases also participate in non-apoptotic processes. In the present study, we investigated activation (cleavage) of caspase-7 in mouse hair follicles and surrounding tissue during embryonic development into adulthood. Casp7 −/− mice were examined to understand the effect of caspase-7 deficiency in the skin. The activated form of caspase-7 was observed during embryonic hair follicle development, as well as in the first hair cycle. In general, activation of caspase-7 did not correlate with apoptosis and activation of caspase-3, except during physiological hair follicle regression. Notably, cleaved caspase-7 was observed in mast cells and its deficiency in the adult skin resulted in increased mast cell number. Our study shows for the first time activated caspase-7 in hair follicles and mast cells and indicates its non-apoptotic roles in the skin.

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References

  • Botchkarev VA, Eichmüller S, Peters EM, Pietsch P, Johansson O, Maurer M, Paus R (1997) A simple immunofluorescence technique for simultaneous visualization of mast cells and nerve fibers reveals selectivity and hair cycle–dependent changes in mast cell–nerve fiber contacts in murine skin. Arch Dermatol Res 289:292–302

    Article  CAS  PubMed  Google Scholar 

  • Botchkareva NV, Ahluwalia G, Shander D (2006) Apoptosis in the hair follicle. J Invest Dermatol 126:258–264

    Article  CAS  PubMed  Google Scholar 

  • Dahlin JS, Hallgren J (2015) Mast cell progenitors: origin, development and migration to tissues. Mol Immunol 63:9–17. doi:10.1016/j.molimm.2014.01.018

    Article  CAS  PubMed  Google Scholar 

  • de la Cadena SG, Hernández-Fonseca K, Camacho-Arroyo I, Massieu L (2014) Glucose deprivation induces reticulum stress by the PERK pathway and caspase-7- and calpain-mediated caspase-12 activation. Apoptosis 19:414–427. doi:10.1007/s10495-013-0930-7

    Article  PubMed  Google Scholar 

  • de Rivero Vaccari JP, Sawaya ME, Brand F 3rd, Nusbaum BP, Bauman AJ, Bramlett HM, Dietrich WD, Keane RW (2012) Caspase-1 level is higher in the scalp in androgenetic alopecia. Dermatol Surg 38:1033–1039. doi:10.1111/j.1524-4725.2012.02378.x

    Article  PubMed  Google Scholar 

  • Duprez L, Takahashi N, Van Hauwermeiren F, Vandendriessche B, Goossens V, Vanden Berghe T, Declercq W, Libert C, Cauwels A, Vandenabeele P (2011) RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity 35:908–918. doi:10.1016/j.immuni.2011.09.020

    Article  CAS  PubMed  Google Scholar 

  • Eckhart L, Declercq W, Ban J, Rendl M, Lengauer B, Mayer C, Lippens S, Vandenabeele P, Tschachler E (2000) Terminal differentiation of human keratinocytes and stratum corneum formation is associated with caspase-14 activation. J Invest Dermatol 115:1148–1151

    Article  CAS  PubMed  Google Scholar 

  • Erener S, Pétrilli V, Kassner I, Minotti R, Castillo R, Santoro R, Hassa PO, Tschopp J, Hottiger MO (2012) Inflammasome-activated caspase 7 cleaves PARP1 to enhance the expression of a subset of NF-κB target genes. Mol Cell 46:200–211. doi:10.1016/j.molcel.2012.02.016

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Faroldi G, Melo FR, Rönnberg E, Grujic M, Pejler G (2013) Active caspase-3 is stored within secretory compartments of viable mast cells. J Immunol 191:1445–1452. doi:10.4049/jimmunol.1300216

    Article  CAS  PubMed  Google Scholar 

  • Kovalenko A, Kim JC, Kang TB, Rajput A, Bogdanov K, Dittrich-Breiholz O, Kracht M, Brenner O, Wallach D (2009) Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease. J Exp Med 206:2161–2177. doi:10.1084/jem.20090616

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lakhani SA, Masud A, Kuida K, Porter GA Jr, Booth CJ, Mehal WZ, Inayat I, Flavell RA (2006) Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. Science 311:847–857

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lamkanfi M, Kanneganti TD (2010) Caspase-7: a protease involved in apoptosis and inflammation. Int J Biochem Cell Biol 42:21–24. doi:10.1016/j.biocel.2009.09.013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T, Vandenabeele P (2007) Caspases in cell survival, proliferation and differentiation. Cell Death Differ 14:44–55

    Article  CAS  PubMed  Google Scholar 

  • Lin CM, Yuan YP, Chen XC, Li HH, Cai BZ, Liu Y, Zhang H, Li Y, Huang K (2015) Expression of Wnt/β-catenin signaling, stem-cell markers and proliferating cell markers in rat whisker hair follicles. J Mol Histol 46:233–240. doi:10.1007/s10735-015-9616-5

    Article  CAS  PubMed  Google Scholar 

  • Lindner G, Botchkarev VA, Botchkareva NV, Ling G, van der Veen C, Paus R (1997) Analysis of apoptosis during hair follicle regression (catagen). Am J Pathol 151:1601–1617

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lippens S, Kockx M, Knaapen M, Mortier L, Polakowska R, Verheyen A, Garmyn M, Zwijsen A, Formstecher P, Huylebroeck D, Vandenabeele P, Declercq W (2000) Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing. Cell Death Differ 7:1218–1224

    Article  CAS  PubMed  Google Scholar 

  • Lippens S, Hoste E, Vandenabeele P, Agostinis P, Declercq W (2009) Cell death in the skin. Apoptosis 14:549–556. doi:10.1007/s10495-009-0324-z

    Article  PubMed  Google Scholar 

  • Lüthi AU, Cullen SP, McNeela EA, Duriez PJ, Afonina IS, Sheridan C, Brumatti G, Taylor RC, Kersse K, Vandenabeele P, Lavelle EC, Martin SJ (2009) Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity 31:84–98. doi:10.1016/j.immuni.2009.05.007

    Article  PubMed  Google Scholar 

  • Magerl M, Tobin DJ, Müller-Röver S, Hagen E, Lindner G, McKay IA, Paus R (2001) Patterns of proliferation and apoptosis during murine hair follicle morphogenesis. J Invest Dermatol 116:947–955

    Article  CAS  PubMed  Google Scholar 

  • Matalova E, Vanden Berghe T, Svandova E, Vandenabeele P, Healy C, Sharpe PT, Tucker AS (2012) Caspase-7 in molar tooth development. Arch Oral Biol 57:1474–1481. doi:10.1016/j.archoralbio.2012.06.009

    Article  CAS  PubMed  Google Scholar 

  • Maurer M, Fischer E, Handjiski B, von Stebut E, Algermissen B, Bavandi A, Paus R (1997) Activated skin mast cells are involved in murine hair follicle regression (catagen). Lab Invest 77:319–332

    CAS  PubMed  Google Scholar 

  • Müller-Röver S, Handjiski B, van der Veen C, Eichmüller S, Foitzik K, McKay IA, Stenn KS, Paus R (2001) A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol 117:3–15

    Article  PubMed  Google Scholar 

  • Okuyama R, Nguyen BC, Talora C, Ogawa E, Tommasi di Vignano A, Lioumi M, Chiorino G, Tagami H, Woo M, Dotto GP (2004) High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism. Dev Cell 6:551–562

    Article  CAS  PubMed  Google Scholar 

  • Ramuz O, Isnardon D, Devilard E, Charafe-Jauffret E, Hassoun J, Birg F, Xerri L (2003) Constitutive nuclear localisation and initial cytoplasmic apoptotic activation of endogenous caspase-3 evidenced by confocal microscopy. Int J Exp Pathol 84:75–81

    Article  PubMed Central  PubMed  Google Scholar 

  • Sabatino G, Nicoletti M, Neri G, Saggini A, Rosati M, Conti F, Cianchetti E, Toniato E, Fulcheri M, Caraffa A, Antinolfi P, Frydas S, Pandolfi F, Potalivo G, Galzio R, Conti P, Theoharides TC (2012) Impact of IL-9 and IL-33 in mast cells. J Biol Regul Homeost Agents 26:577–586

    CAS  PubMed  Google Scholar 

  • Saluja R, Hawro T, Eberle J, Church MK, Maurer M (2014) Interleukin-33 promotes the proliferation of mouse mast cells through ST2/MyD88 and p38 MAPK-dependent and kit-independent pathways. J Biol Regul Homeost Agents 28:575–585

    CAS  PubMed  Google Scholar 

  • Schneider MR, Schmidt-Ullrich R, Paus R (2009) The hair follicle as a dynamic miniorgan. Curr Biol 19:R132–R142. doi:10.1016/j.cub.2008.12.005

    Article  CAS  PubMed  Google Scholar 

  • Soma T, Ogo M, Suzuki J, Takahashi T, Hibino T (1998) Analysis of apoptotic cell death in human hair follicles in vivo and in vitro. J Invest Dermatol 111:948–954

    Article  CAS  PubMed  Google Scholar 

  • Svandova E, Lesot H, Vanden Berghe T, Tucker AS, Sharpe PT, Vandenabeele P, Matalova E (2014) Non-apoptotic functions of caspase-7 during osteogenesis. Cell Death Dis 5:e1366. doi:10.1038/cddis.2014.330

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Takahashi T, Ogo M, Hibino T (1998) Partial purification and characterization of two distinct types of caspases from human epidermis. J Invest Dermatol 111:367–372

    Article  CAS  PubMed  Google Scholar 

  • Vesela B, Matalova E (2015) Expression of apoptosis-related genes in the mouse skin during the first postnatal catagen stage, focused on localisation of Bnip3L and caspase-12. Connect Tissue Res 56:326–335. doi:10.3109/03008207.2015.1040546

    Article  CAS  PubMed  Google Scholar 

  • Yaoita Y (2002) Inhibition of nuclear transport of caspase-7 by its prodomain. Biochem Biophys Res Commun 291:79–84

    Article  CAS  PubMed  Google Scholar 

  • Zhivotovsky B, Samali A, Gahm A, Orrenius S (1999) Caspases: their intracellular localization and translocation during apoptosis. Cell Death Differ 6:644–651

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Recent research in Brno labs runs under the Centre of Excellence of the Grant Agency of the Czech Republic (14-37368G). International cooperation with UK was granted by Academy of Science of the CR (M200451201). The IAPG labs are financed from the RVO 67985904.

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Authors and Affiliations

  1. Institute of Animal Physiology and Genetics CAS, v.v.i., Veveri 97, 602 00, Brno, Czech Republic

    Barbora Vesela, Eva Svandova & Eva Matalova

  2. Department of Experimental Biology, Masaryk University, Brno, Czech Republic

    Barbora Vesela

  3. Inflammation Research Center, VIB, 9000, Ghent, Belgium

    Tom Vanden Berghe & Peter Vandenabeele

  4. Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium

    Tom Vanden Berghe & Peter Vandenabeele

  5. Department of Craniofacial Development and Stem Cell Biology, King‘s College London, London, UK

    Abigail S. Tucker

  6. Department of Physiology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic

    Eva Matalova

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  1. Barbora Vesela
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  2. Eva Svandova
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  3. Tom Vanden Berghe
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  4. Abigail S. Tucker
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  5. Peter Vandenabeele
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  6. Eva Matalova
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Correspondence to Barbora Vesela.

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Vesela, B., Svandova, E., Berghe, T.V. et al. Non-apoptotic role for caspase-7 in hair follicles and the surrounding tissue. J Mol Hist 46, 443–455 (2015). https://doi.org/10.1007/s10735-015-9636-1

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  • DOI: https://doi.org/10.1007/s10735-015-9636-1

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