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Wound healing with topical BRAF inhibitor therapy in a diabetic model suggests tissue regenerative effects.

Publication ,  Journal Article
Escuin-Ordinas, H; Liu, Y; Sun, L; Hugo, W; Dimatteo, R; Huang, RR; Krystofinski, P; Azhdam, A; Lee, J; Comin-Anduix, B; Cochran, AJ; Lo, RS ...
Published in: PloS one
January 2021

Wound healing is a multi-step process to rapidly restore the barrier function. This process is often impaired in diabetic patients resulting in chronic wounds and amputation. We previously found that paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway via topical administration of the BRAF inhibitor vemurafenib accelerates wound healing by activating keratinocyte proliferation and reepithelialization pathways in healthy mice. Herein, we investigated whether this wound healing acceleration also occurs in impaired diabetic wounds and found that topical vemurafenib not only improves wound healing in a murine diabetic wound model but unexpectedly promotes hair follicle regeneration. Hair follicles expressing Sox-9 and K15 surrounded by CD34+ stroma were found in wounds of diabetic and non-diabetic mice, and their formation can be prevented by blocking downstream MEK signaling. Thus, topically applied BRAF inhibitors may accelerate wound healing, and promote the restoration of improved skin architecture in both normal and impaired wounds.

Duke Scholars

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2021

Volume

16

Issue

6

Start / End Page

e0252597

Related Subject Headings

  • beta Catenin
  • Wound Healing
  • Wnt Signaling Pathway
  • Vemurafenib
  • Skin
  • Regeneration
  • Proto-Oncogene Proteins B-raf
  • Protein Kinase Inhibitors
  • Mice, Obese
  • Mice, Inbred BALB C
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Escuin-Ordinas, H., Liu, Y., Sun, L., Hugo, W., Dimatteo, R., Huang, R. R., … Ribas, A. (2021). Wound healing with topical BRAF inhibitor therapy in a diabetic model suggests tissue regenerative effects. PloS One, 16(6), e0252597. https://doi.org/10.1371/journal.pone.0252597
Escuin-Ordinas, Helena, Yining Liu, Lu Sun, Willy Hugo, Robert Dimatteo, Rong Rong Huang, Paige Krystofinski, et al. “Wound healing with topical BRAF inhibitor therapy in a diabetic model suggests tissue regenerative effects.PloS One 16, no. 6 (January 2021): e0252597. https://doi.org/10.1371/journal.pone.0252597.
Escuin-Ordinas H, Liu Y, Sun L, Hugo W, Dimatteo R, Huang RR, et al. Wound healing with topical BRAF inhibitor therapy in a diabetic model suggests tissue regenerative effects. PloS one. 2021 Jan;16(6):e0252597.
Escuin-Ordinas, Helena, et al. “Wound healing with topical BRAF inhibitor therapy in a diabetic model suggests tissue regenerative effects.PloS One, vol. 16, no. 6, Jan. 2021, p. e0252597. Epmc, doi:10.1371/journal.pone.0252597.
Escuin-Ordinas H, Liu Y, Sun L, Hugo W, Dimatteo R, Huang RR, Krystofinski P, Azhdam A, Lee J, Comin-Anduix B, Cochran AJ, Lo RS, Segura T, Scumpia PO, Ribas A. Wound healing with topical BRAF inhibitor therapy in a diabetic model suggests tissue regenerative effects. PloS one. 2021 Jan;16(6):e0252597.

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2021

Volume

16

Issue

6

Start / End Page

e0252597

Related Subject Headings

  • beta Catenin
  • Wound Healing
  • Wnt Signaling Pathway
  • Vemurafenib
  • Skin
  • Regeneration
  • Proto-Oncogene Proteins B-raf
  • Protein Kinase Inhibitors
  • Mice, Obese
  • Mice, Inbred BALB C