Hoxc13 is a crucial regulator of murine hair cycle

详细信息    查看全文

• 作者：Weiming Qiu ; Mingxing Lei ; Hui Tang ; Hongtao Yan ; Xuhong Wen…
• 关键词：Hoxc13 ; Hair cycle ; Apoptosis ; Proliferation ; Phosphorylated smad2
• 刊名：Cell and Tissue Research
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：364
• 期：1
• 页码：149-158
• 全文大小：1,353 KB
• 参考文献：Alonso L, Fuchs E (2006) The hair cycle. J Cell Sci 119:391–393CrossRef PubMed
  Foitzik K, Lindner G, Mueller-Roever S, Maurer M, Botchkareva N, Botchkarev V, Handjiski B, Metz M, Hibino T, Soma T, Dotto GP, Paus R (2000) Control of murine hair follicle regression (catagen) by TGF-beta1 in vivo. FASEB J 14:752–760PubMed
  Godwin AR, Capecchi MR (1998) Hoxc13 mutant mice lack external hair. Genes Dev 12:11–20CrossRef PubMed PubMedCentral
  Hwang J, Mehrani T, Millar SE, Morasso MI (2008) Dlx3 is a crucial regulator of hair follicle differentiation and cycling. Development 135:3149–3159CrossRef PubMed PubMedCentral
  Jave-Suarez LF, Winter H, Langbein L, Rogers MA, Schweizer J (2002) HOXC13 is involved in the regulation of human hair keratin gene expression. J Biol Chem 277:3718–3726CrossRef PubMed
  Jing J, Wu XJ, Li YL, Cai SQ, Zheng M, Lu ZF (2014) Expression of decorin throughout the murine hair follicle cycle: hair cycle dependence and anagen phase prolongation. Exp Dermatol 23:486–491CrossRef PubMed
  Kasiri S, Ansari KI, Hussain I, Bhan A, Mandal SS (2013) Antisense oligonucleotide mediated knockdown of HOXC13 affects cell growth and induces apoptosis in tumor cells and over expression of HOXC13 induces 3D-colony formation. RSC Adv 3:3260–3269CrossRef PubMed PubMedCentral
  Kwack MH, Kim MK, Kim JC, Sung YK (2012) Dickkopf 1 promotes regression of hair follicles. J Investig Dermatol 132:1554–1560CrossRef PubMed
  Li J, Jiang TX, Chuong CM (2013) Many paths to alopecia via compromised regeneration of hair follicle stem cells. J Investig Dermatol 133:1450–1452CrossRef PubMed PubMedCentral
  Lin Z, Chen Q, Shi L, Lee M, Giehl KA, Tang Z, Wang H, Zhang J, Yin J, Wu L, Xiao R, Liu X, Dai L, Zhu X, Li R, Betz RC, Zhang X, Yang Y (2012) Loss-of-function mutations in HOXC13 cause pure hair and nail ectodermal dysplasia. Am J Hum Genet 91:906–911CrossRef PubMed PubMedCentral
  Massague J (1998) TGF-beta signal transduction. Annu Rev Biochem 67:753–791CrossRef PubMed
  Muller-Rover S, Handjiski B, van der Veen C, Eichmuller 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 Investig Dermatol 117:3–15CrossRef PubMed
  Niimori D, Kawano R, Felemban A, Niimori-Kita K, Tanaka H, Ihn H, Ohta K (2012) Tsukushi controls the hair cycle by regulating TGF-beta1 signaling. Dev Biol 372:81–87CrossRef PubMed
  Oda Y, Hu L, Bul V, Elalieh H, Reddy JK, Bikle DD (2012) Coactivator MED1 ablation in keratinocytes results in hair-cycling defects and epidermal alterations. J Investig Dermatol 132:1075–1083CrossRef PubMed PubMedCentral
  Paus R, Handjiski B, Eichmüller S, Czarnetzki BM (1994) Chemotherapy-induced alopecia in mice. Induction by cyclophosphamide, inhibition by cyclosporine A, and modulation by DEX. Am J Pathol 1994 144:719–734
  Pruett ND, Tkatchenko TV, Jave-Suarez L, Jacobs DF, Potter CS, Tkatchenko AV, Schweizer J, Awgulewitsch A (2004) Krtap16, characterization of a new hair keratin-associated protein (KAP) gene complex on mouse chromosome 16 and evidence for regulation by Hoxc13. J Biol Chem 279:51524–51533CrossRef PubMed
  Qiu W, Lei M, Li J, Wang N, Lian X (2014) Activated hair follicle stem cells and Wnt/beta-catenin signaling involve in pathnogenesis of sebaceous neoplasms. Int J Med Sci 11:1022–1028CrossRef PubMed PubMedCentral
  Soma T, Tsuji Y, Hibino T (2002) Involvement of transforming growth factor-beta2 in catagen induction during the human hair cycle. J Investig Dermatol 118:993–997CrossRef PubMed
  Soma T, Dohrmann CE, Hibino T, Raftery LA (2003) Profile of transforming growth factor-beta responses during the murine hair cycle. J Investig Dermatol 121:969–975CrossRef PubMed
  Stelnicki EJ, Komuves LG, Kwong AO, Holmes D, Klein P, Rozenfeld S, Lawrence HJ, Adzick NS, Harrison M, Largman C (1998) HOX homeobox genes exhibit spatial and temporal changes in expression during human skin development. J Investig Dermatol 110:110–115CrossRef PubMed
  Stenn KS, Paus R (2001) Controls of hair follicle cycling. Physiol Rev 81:449–494PubMed
  Thummel R, Li L, Tanase C, Sarras MP Jr, Godwin AR (2004) Differences in expression pattern and function between zebrafish hoxc13 orthologs: recruitment of Hoxc13b into an early embryonic role. Dev Biol 274:318–333CrossRef PubMed
  Tkatchenko AV, Visconti RP, Shang L, Papenbrock T, Pruett ND, Ito T, Ogawa M, Awgulewitsch A (2001) Overexpression of Hoxc13 in differentiating keratinocytes results in downregulation of a novel hair keratin gene cluster and alopecia. Development 128:1547–1558PubMed
  Williams TM, Williams ME, Heaton JH, Gelehrter TD, Innis JW (2005) Group 13 HOX proteins interact with the MH2 domain of R-Smads and modulate Smad transcriptional activation functions independent of HOX DNA-binding capability. Nucleic Acids Res 33:4475–4484CrossRef PubMed PubMedCentral
  
• 作者单位：Weiming Qiu (1)
  Mingxing Lei (2)
  Hui Tang (1)
  Hongtao Yan (1)
  Xuhong Wen (1)
  Wei Zhang (1)
  Ranjing Tan (1)
  Duan Wang (1)
  Jinjin Wu (1)
  
  1. Department of Dermatology, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China
  2. “111” Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing, 400044, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Human Genetics
  Proteomics
  Molecular Medicine
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0878

文摘

Hair follicles undergo cyclical growth and regression during postnatal life. Hair regression is an apoptosis-driven process strictly controlled by micro- and macro-environmental signals. However, how these signals are controlled remains largely unknown. Hoxc13, a member of the Hox gene family, is reported to play an important role in hair follicle differentiation. In the present study, we observed that Hoxc13 was highly expressed in the outer root sheath, matrix, medulla and inner root sheath of hair follicles in a hair cycle-dependent manner. We therefore investigated the role of Hoxc13 in hair follicle cycling. Injection of ShRNA (ShHoxc13) to suppress Hoxc13 in early anagen promoted premature catagen entry, shown by significantly decreased hair length and hair bulb size, increased percentage of catagen hair follicles, hair cycle score and TUNEL+ cells and inhibited proliferation. In contrast, local injection of recombinant Hoxc13 polypeptide (rhHoxc13) during the late anagen phase prolonged the anagen phase. Additionally, rhHoxc13 injections during the telogen phase significantly promoted hair growth and induced the anagen progression. At the molecular level, the expression of phosphorylated smad2 (p-smad2), a key factor of active TGF-β1 signaling, was up-regulated in the ShHoxc13-treated hair follicles and down-regulated in rhHoxc13-treated hair follicles, suggesting that Hoxc13 might block anagen–catagen transition by inhibiting the TGF-β1 signaling. Taken together, our data strongly suggest that Hoxc13 is a novel and crucial regulator of the hair cycle. This might also provide an understanding of the mechanism of the ‘hair cycle clock’ and the development of alopecia treatments.