Cell and Tissue Research

, Volume 364, Issue 1, pp 149–158 | Cite as

Hoxc13 is a crucial regulator of murine hair cycle

  • Weiming Qiu
  • Mingxing Lei
  • Hui Tang
  • Hongtao Yan
  • Xuhong Wen
  • Wei Zhang
  • Ranjing Tan
  • Duan Wang
  • Jinjin WuEmail author
Regular Article


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.


Hoxc13 Hair cycle Apoptosis Proliferation Phosphorylated smad2 



Dickkopf 1


Inner root sheath


Outer root sheath


Polyacrylamide gel electrophoresis


Phosphate-buffered saline


Polyvinylidene fluoride



This work was supported by grants from the National Nature Science Foundation of China (Grant number: 31170924) and Fundamental Research Funds for the Central Universities (106112015CDJRC231206) to Mingxing Lei. We thank Dr. Randall B. Widelitz (University of Southern California) for carefully revising the manuscript.

Supplementary material

441_2015_2312_MOESM1_ESM.doc (10.7 mb)
ESM 1 (DOC 11005 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • 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
    Email author
  1. 1.Department of Dermatology, Daping HospitalThe Third Military Medical UniversityChongqingChina
  2. 2.“111” Project Laboratory of Biomechanics and Tissue Repair, College of BioengineeringChongqing UniversityChongqingChina

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