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 language | English |
|---|---|
| Pages (from-to) | 764-770 |
| Number of pages | 7 |
| Journal | Journal of Dental Research |
| Volume | 91 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2012 |
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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 journal › Article
}
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 -