title: Post-transcriptional Regulation of Keratinocyte Progenitor Cell Expansion, Differentiation and Hair Follicle Regression by miR-22.
abstract: Hair follicles (HF) undergo precisely regulated recurrent cycles of growth, cessation, and rest. The transitions from anagen (growth), to catagen (regression), to telogen (rest) involve a physiological involution of the HF. This process is likely coordinated by a variety of mechanisms including apoptosis and loss of growth factor signaling. However, the precise molecular mechanisms underlying follicle involution after hair keratinocyte differentiation and hair shaft assembly remain poorly understood. Here we demonstrate that a highly conserved microRNA, miR-22 is markedly upregulated during catagen and peaks in telogen. Using gain- and loss-of-function approaches in vivo, we find that miR-22 overexpression leads to hair loss by promoting anagen-to-catagen transition of the HF, and that deletion of miR-22 delays entry to catagen and accelerates the transition from telogen to anagen. Ectopic activation of miR-22 results in hair loss due to the repression a hair keratinocyte differentiation program and keratinocyte progenitor expansion, as well as promotion of apoptosis. At the molecular level, we demonstrate that miR-22 directly represses numerous transcription factors upstream of phenotypic keratin genes, including Dlx3, Foxn1, and Hoxc13. We conclude that miR-22 is a critical post-transcriptional regulator of the hair cycle and may represent a novel target for therapeutic modulation of hair growth.
authors.affiliation: State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China; Department of Biochemistry and Molecular Biology, Basic Medical College, Tianjin Medical University, Tianjin, China; Department of Animal Science, Southwest University, Rongchang, Chongqing, China.
authors.forename: Shukai
authors.initials: S
authors.lastname: Yuan
authors.affiliation: State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.affiliation: State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Meng
authors.affiliation: State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Chongqing Academy of Animal Science, Rongchang, Chongqing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Beijing, China.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Beijing, China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Xue
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lengner
authors.affiliation: State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors.forename: Zhengquan
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000505:Alopecia / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; D007633:Keratins