title: The epidermal Integrin beta-1 and p75NTR positive cells proliferating and migrating during wound healing produce various growth factors, while the expression of p75NTR is decreased in patients with chronic skin ulcers.
abstract: BACKGROUND
  More effective treatment strategies are needed for the chronic skin ulcers. Recently, it has been reported that clinical application of stem cells improve wound healing.
  
  
  OBJECTIVE
  We aimed to determine the dynamic time-course movement of epidermal stem cell markers especially p75 neurotrophin receptor (p75NTR) and Integrin beta-1 in wound healing process. Furthermore, we also investigated the presence of these markers in human.
  
  
  METHODS
  Epidermal Integrin beta-1(+) and p75NTR(+) cells were counted in wound healing process in mice. Both cells were also counted in human skin specimen obtained from chronic skin ulcers and healthy controls. Growth factor gene expression levels by purified mouse epidermal p75NTR(+) cells were also analyzed using real-time RT-PCR.
  
  
  RESULTS
  Integrin beta-1(+) and p75NTR(+) cells were proliferated from 3 days after wounding. Reepithelization was completed 7 days after wounding, and the numbers of cells were returned to the baseline levels by 14 days after wounding. Integrin beta-1(+) cells were proliferated in the basal layer, and p75NTR(+) cells were proliferated in the upper layer of epidermis. In human skin, Integrin beta-1(+) and p75NTR(+) cells were 81%±12% and 36%±15% of the basal cells, respectively. In patients with chronic skin ulcers, the percentage of Integrin beta-1(+) cells in the epidermis was identical to healthy controls. Surprisingly, p75NTR(+) cells were significantly decreased in chronic skin ulcer patients (1.2%±2.6%; p<0.0005) compared to healthy controls. Purified mouse epidermal p75NTR(+) cells expressed higher transforming growth factor-beta2 and vascular endothelial growth factor-alpha transcripts and lower epidermal growth factor transcripts than p75NTR(-) cells.
  
  
  CONCLUSIONS
  These results suggest that Integrin beta-1(+) and p75NTR(+) cells play an important role in wound healing process, and that p75NTR may be a key molecule and a candidate for new therapeutic target besides preexisting molecules for chronic skin ulcer patients.
authors: Department of Dermatology, Fujita Health University School of Medicine, 1-98 Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. iwayou@fujita-hu.ac.jp
authors: Yohei
authors: Y
authors: Iwata
authors: Hirohiko
authors: H
authors: Akamatsu
authors: Seiji
authors: S
authors: Hasegawa
authors: Masayuki
authors: M
authors: Takahashi
authors: Akiko
authors: A
authors: Yagami
authors: Satoru
authors: S
authors: Nakata
authors: Kayoko
authors: K
authors: Matsunaga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D012883:Skin Ulcer / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
chemical_list: D019012:Integrin beta1; D036341:Intercellular Signaling Peptides and Proteins; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse
keywords: CD271; CD29; Integrin beta-1; Stem cell; Wound healing; p75NTR