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follicles, and participates in the formation of the root sheath.  Conflicts of interest
                                                             There are no conflicts of interest.
         In  an  attempt  to  improve  our  understanding  of  the  role  of
         β-catenin in HFSC proliferation and differentiation, this study   REFERENCES
         investigated whether KGF treatment stimulates these processes
         via the Wnt signaling pathway. The results indicate that adding   1.   Yang  B, Xiang  MJ. Regulation  of Wnt signaling  pathway involved  in the
         KGF to serum-free culture medium containing EGF stimulated   differentiation of hair follicle stem cells induced by lithium chloride. Zhongguo
         HFSC proliferation. Although this effect was not apparent in   Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2011;15:9202-6.
         the first 48 h of culture, for incubation times more than 48 h,   2.   Taylor G, Lehrer MS, Jensen PJ, Sun TT, Lavker RM. Involvement of follicular stem
         there was a marked difference in DNA content between the 10   cells in forming not only the follicle but also the epidermise. Cell 2000;102:451-61.
         µg/L KGF treatment group and control cells. The reduction in   3.   Waikel RL, Kawachi Y, Waikel PA, Wang XJ, Roop DR. Deregulated expression of
         DNA content indicates that KGF maintains cell proliferation and   c-Myc depletes epidermal stem cells. Nat Genet 2001;28:165- 8.
         postpones keratinocyte differentiation.             4.   DasGupta R, Kaykas A, Moon RT, Perrimon N. Functional genomic analysis of the
                                                                 Wnt-wingless signaling pathway. Science 2005;308:826-33.
                                                             5.   Michel M, Török N, Godbout MJ, Lussier M, Gaudreau P, Royal A, Germain L.
                      [6]
         Richardson et al.  observed repression of hair follicle induction   Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: keratin 19
         by KGF and EGF in cultured mice embryo skin. They found   expressing cells are differentially localized in function of anatomic sites, and their
         that Wnt signaling plays a role in the initial formation of hair   number varies with donor age and culture stage. J Cell Sci 1996;109:1017-28.
         follicles, and that the latter stages of follicle formation are   6.   Richardson GD, Bazzi H, Fantauzzo KA, Waters JM, Crawford H, Hynd P,
         dependent on the Shh signal. Formation of the hair follicle is   Christiano  AM, Jahoda  CA. KGF and  EGF signalling block hair follicle
         usually caused by activation of Wnt signaling and upregulation   induction and promote interfollicular epidermal fate in developing mouse
         of β-catenin mRNA. The Shh activating signal also elevates Gli1   skin. Development 2009;136:2153-64.
         mRNA. Nuclear LEF1 expression occurs at the initial stages and   7.   Mullis KB, Faloona FA. Specific synthesis of DNA in vitro via a polymerase-
         increases after 24 h. However, epidermal cells induced by KGF   8.   catalyzed chain reaction. Methods Enzymol 1987;155:335-50.
                                                                 Watt FM. Epidermal stem cells: markers, patterning and the control of stem
         or EGF contain high nuclear LEF1 expression at all time points.   cell fate. Philos Trans R Soc Lond B Biol Sci 1998;353:831-7.
         KGF and EGF noticeably inhibited several important signaling   9.   Commo S, Gaillard O, Bernard BA. The human hair follicle contains two
         molecules  produced  by  hair  follicles,  including  Wnt  (LEF1,   distinct K19 positive compartments in the outer root sheath: a unifying
         DKK4), Shh single pathway, and delayed HFSC differentiation.   hypothesis for stem cell reservoir. Differentiation 2000;66:157-64.
         Recently, Andreadis et al.  using a skin equivalent model system,   10.  Widelitz RB. Wnt signaling in skin organogenesis. Organogenesis 2008;4:123-3.
                           [21]
         demonstrated that KGF significantly facilitates the proliferation   11.  Lapébie P, Gazave E, Ereskovsky A, Derelle R, Bézac C, Renard E, Houliston
         of epidermal cells inoculated in a cellular dermal matrix, which   E, Borchiellini  C. Wnt/β-catenin signaling and  epithelial  patterning in the
                                                                 homoscleromorph sponge oscarella. PLoS One 2009;4:1-6.
         is associated with induced expression of  α5β1 integrins and   12.  Lowell S, Jones P, Le Roux I, Dunne J, Watt FM. Stimulation of human
         delayed keratin-10 expression. In the present study, HFSCs were   epidermal differentiation by delta-notch signaling at the boundaries of stem-
         observed to exhibit a low proliferation rate in the first 72 h after   cell clusters. Curr Biol 2000;10:491-500.
         KGF treatment, especially in the 10 µg/L treatment group. When   13.  Marchese C, Chedid M, Dirsch OR, Csaky KG, Santanelli F, Latini C, LaRochelle
         the culture time was longer than 72 h, DNA measurements   WJ, Torrisi MR, Aaronson SA. Modulation of keratinocyte growth factor and
         showed that KGF treatment postponed apoptosis, but that high   its receptor in reepithelializing human skin. J Exp Med 1995;182:1369-76.
         KGF concentrations accelerated cell aging. This may be related to   14.  Wexler EM, Geschwind DH, Palmer TD. Lithium regulates adult hippocampal
         excessive nutrient consumption in the in vitro culture medium.   progenitor  development  through  canonical Wnt  pathway activation.  Mol
                                                                 Psychiatry 2008;13:285-92.
         In cells treated with 10 µg/L KGF β-catenin expression increased   15.  Rao  AS, Kremenevskaja  N, Resch  J, Brabant  G. Lithium stimulates
         slightly and GSK-3β expression decreased on day 7, as HFSCs   proliferation in cultured thyroeytes by activating Wnt/beta-catenin signalling.
         underwent differentiation. LEF1 levels, however, declined at an   Eur J Endocrina1 2005;153:929-38.
         early stage. How KGF switches the Wnt/β-catenin pathway from   16.  Hsu SC, Galceran J, Grosschedl R. Modulation of transcriptional regulation
         an activated state to an inhibited state is unclear. However, this   by LEF-1 in response to Wnt-1 signaling and association with beta-Catenin.
         data  suggest that KGF  concentration inversely correlates   Mol Cell Biol 1998;18:4807-18.
         with LEF1 expression and represses HFSC differentiation and   17.  Zhu AJ, Watt FM. Beta-catenin signaling modulates  proliferative potential
         the formation of hair follicles. This result supports a direct   of human epidermal keratinocytes independently of intercellular adhesion.
                                                                 Development 1999;126:2285-98.
         association of KGF with the Wnt signaling pathway through   18.  DasGupta  R, Rhee H, Fuchs E. A developmental conundrum: astabilized
         reducing LEF1 levels. These data are consistent with the   form of beta - catenin lacking the transcriptional activation domain triggers
         results of Richardson et al.  However, some of the links that   features of hair cell fate in epidermal cells and epidermal cell fate in hair
                              [6]
         mediate KGF regulation of the Wnt signaling pathway are   follicle cells. J Cell Biol 2002;158:331-44.
         not yet clear and require further investigation.    19.  Nguyen H, Rendl M, Fuchs E. Tcf3 governs stem cell features and represses
                                                                 cell fate determination in skin. Cell 2006;10:171-83.
         Financial support and sponsorship                   20.  Fathke C, Wilson L, Shah K, Kim B, Hocking A, Moon R, Isik F. Wnt signaling induces
                                                                 epithelial differentiation during cutaneous wound healing. BMC Cell Biol 2006;7:4.
         This  study is  supported by  the  National Natural  Science   21.  Andreadis ST, Hamoen KE, Yarmush ML, Morgan JR. Keratinocyte growth
         Foundation of China (No.30772099) and Beijing Municipal   factor  induces hyperproliferation and  delays differentiation in a skin
         Natural Science Foundation (No.7112111).                equivalent model system. FASEB J 2001;15:898-906.







         46                                                                  Plast Aesthet Res || Vol 3 || Issue 2  || Feb 29, 2016
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