Smad2 decelerates re-epithelialization during gingival wound healing

K. Tomikawa, Tadashi Yamamoto, N. Shiomi, M. Shimoe, S. Hongo, Keisuke Yamashiro, T. Yamaguchi, H. Maeda, Shogo Takashiba

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

During periodontal regeneration, inhibition of gingival downgrowth is necessary to promote migration of mesenchymal cells into the defects. Transforming growth factor (TGF)-Î is a pleiotropic cytokine that has numerous cell functions, including regulation of epithelial growth. Recent studies have shown that Smad2, a downstream transcription factor of TGF-Î, plays crucial roles in wound healing in the epithelia. Therefore, we investigated the effects of Smad2 overexpression on re-epithelialization of gingival wounds. Transgenic mice overexpressing smad2 driven by the keratin 14 promoter (k14-smad2) were confirmed to have significant Smad2 phosphorylation in gingival basal epithelia. Punch wounds were made in the palatal gingiva, and wound healing was assessed histologically for 7 days. Re-epithelialization was significantly retarded on day 2, while collagen deposition was enhanced on day 7 in k14-smad2 compared with wild-type mice. Moreover, expression of keratin 16 (K16), an indicator of keratinocyte migration, was significantly inhibited in wound-edge keratinocytes in k14-smad2. The inhibition of K16 coincided with the induction of Smad2 in the corresponding epithelia, while BrdU incorporation was unaffected. These results indicated that Smad2 has inhibitory effects in regulating keratinocyte migration during gingival wound healing. TGF-Î/Smad2 signaling mediating alteration of K16 expression must be tightly regulated during periodontal regeneration.

Original languageEnglish
Pages (from-to)764-770
Number of pages7
JournalJournal of Dental Research
Volume91
Issue number8
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Keratin-16
Re-Epithelialization
Transforming Growth Factors
Keratinocytes
Wound Healing
Epithelium
Regeneration
Wounds and Injuries
Keratin-14
Gingiva
Bromodeoxyuridine
Transgenic Mice
Cell Movement
Transcription Factors
Collagen
Phosphorylation
Cytokines
Growth

Keywords

  • gingival downgrowth
  • keratin 16
  • keratinocyte migration
  • re-epithelialization
  • Smad2
  • wound healing

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Smad2 decelerates re-epithelialization during gingival wound healing. / Tomikawa, K.; Yamamoto, Tadashi; Shiomi, N.; Shimoe, M.; Hongo, S.; Yamashiro, Keisuke; Yamaguchi, T.; Maeda, H.; Takashiba, Shogo.

In: Journal of Dental Research, Vol. 91, No. 8, 08.2012, p. 764-770.

Research output: Contribution to journalArticle

Tomikawa, K. ; Yamamoto, Tadashi ; Shiomi, N. ; Shimoe, M. ; Hongo, S. ; Yamashiro, Keisuke ; Yamaguchi, T. ; Maeda, H. ; Takashiba, Shogo. / Smad2 decelerates re-epithelialization during gingival wound healing. In: Journal of Dental Research. 2012 ; Vol. 91, No. 8. pp. 764-770.
@article{ed7e4bbf6566466696ec20735c0e6413,
title = "Smad2 decelerates re-epithelialization during gingival wound healing",
abstract = "During periodontal regeneration, inhibition of gingival downgrowth is necessary to promote migration of mesenchymal cells into the defects. Transforming growth factor (TGF)-{\^I} is a pleiotropic cytokine that has numerous cell functions, including regulation of epithelial growth. Recent studies have shown that Smad2, a downstream transcription factor of TGF-{\^I}, plays crucial roles in wound healing in the epithelia. Therefore, we investigated the effects of Smad2 overexpression on re-epithelialization of gingival wounds. Transgenic mice overexpressing smad2 driven by the keratin 14 promoter (k14-smad2) were confirmed to have significant Smad2 phosphorylation in gingival basal epithelia. Punch wounds were made in the palatal gingiva, and wound healing was assessed histologically for 7 days. Re-epithelialization was significantly retarded on day 2, while collagen deposition was enhanced on day 7 in k14-smad2 compared with wild-type mice. Moreover, expression of keratin 16 (K16), an indicator of keratinocyte migration, was significantly inhibited in wound-edge keratinocytes in k14-smad2. The inhibition of K16 coincided with the induction of Smad2 in the corresponding epithelia, while BrdU incorporation was unaffected. These results indicated that Smad2 has inhibitory effects in regulating keratinocyte migration during gingival wound healing. TGF-{\^I}/Smad2 signaling mediating alteration of K16 expression must be tightly regulated during periodontal regeneration.",
keywords = "gingival downgrowth, keratin 16, keratinocyte migration, re-epithelialization, Smad2, wound healing",
author = "K. Tomikawa and Tadashi Yamamoto and N. Shiomi and M. Shimoe and S. Hongo and Keisuke Yamashiro and T. Yamaguchi and H. Maeda and Shogo Takashiba",
year = "2012",
month = "8",
doi = "10.1177/0022034512451449",
language = "English",
volume = "91",
pages = "764--770",
journal = "Journal of Dental Research",
issn = "0022-0345",
publisher = "SAGE Publications Inc.",
number = "8",

}

TY - JOUR

T1 - Smad2 decelerates re-epithelialization during gingival wound healing

AU - Tomikawa, K.

AU - Yamamoto, Tadashi

AU - Shiomi, N.

AU - Shimoe, M.

AU - Hongo, S.

AU - Yamashiro, Keisuke

AU - Yamaguchi, T.

AU - Maeda, H.

AU - Takashiba, Shogo

PY - 2012/8

Y1 - 2012/8

N2 - During periodontal regeneration, inhibition of gingival downgrowth is necessary to promote migration of mesenchymal cells into the defects. Transforming growth factor (TGF)-Î is a pleiotropic cytokine that has numerous cell functions, including regulation of epithelial growth. Recent studies have shown that Smad2, a downstream transcription factor of TGF-Î, plays crucial roles in wound healing in the epithelia. Therefore, we investigated the effects of Smad2 overexpression on re-epithelialization of gingival wounds. Transgenic mice overexpressing smad2 driven by the keratin 14 promoter (k14-smad2) were confirmed to have significant Smad2 phosphorylation in gingival basal epithelia. Punch wounds were made in the palatal gingiva, and wound healing was assessed histologically for 7 days. Re-epithelialization was significantly retarded on day 2, while collagen deposition was enhanced on day 7 in k14-smad2 compared with wild-type mice. Moreover, expression of keratin 16 (K16), an indicator of keratinocyte migration, was significantly inhibited in wound-edge keratinocytes in k14-smad2. The inhibition of K16 coincided with the induction of Smad2 in the corresponding epithelia, while BrdU incorporation was unaffected. These results indicated that Smad2 has inhibitory effects in regulating keratinocyte migration during gingival wound healing. TGF-Î/Smad2 signaling mediating alteration of K16 expression must be tightly regulated during periodontal regeneration.

AB - During periodontal regeneration, inhibition of gingival downgrowth is necessary to promote migration of mesenchymal cells into the defects. Transforming growth factor (TGF)-Î is a pleiotropic cytokine that has numerous cell functions, including regulation of epithelial growth. Recent studies have shown that Smad2, a downstream transcription factor of TGF-Î, plays crucial roles in wound healing in the epithelia. Therefore, we investigated the effects of Smad2 overexpression on re-epithelialization of gingival wounds. Transgenic mice overexpressing smad2 driven by the keratin 14 promoter (k14-smad2) were confirmed to have significant Smad2 phosphorylation in gingival basal epithelia. Punch wounds were made in the palatal gingiva, and wound healing was assessed histologically for 7 days. Re-epithelialization was significantly retarded on day 2, while collagen deposition was enhanced on day 7 in k14-smad2 compared with wild-type mice. Moreover, expression of keratin 16 (K16), an indicator of keratinocyte migration, was significantly inhibited in wound-edge keratinocytes in k14-smad2. The inhibition of K16 coincided with the induction of Smad2 in the corresponding epithelia, while BrdU incorporation was unaffected. These results indicated that Smad2 has inhibitory effects in regulating keratinocyte migration during gingival wound healing. TGF-Î/Smad2 signaling mediating alteration of K16 expression must be tightly regulated during periodontal regeneration.

KW - gingival downgrowth

KW - keratin 16

KW - keratinocyte migration

KW - re-epithelialization

KW - Smad2

KW - wound healing

UR - http://www.scopus.com/inward/record.url?scp=84864134711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864134711&partnerID=8YFLogxK

U2 - 10.1177/0022034512451449

DO - 10.1177/0022034512451449

M3 - Article

C2 - 22699208

AN - SCOPUS:84864134711

VL - 91

SP - 764

EP - 770

JO - Journal of Dental Research

JF - Journal of Dental Research

SN - 0022-0345

IS - 8

ER -