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Inhibition of IRE1 results in decreased scar formation
Author(s) -
Boyko Tatiana V.,
Bam Rakesh,
Jiang Dadi,
Wang Zhen,
Bhatia Namrata,
Tran Misha C.,
Longaker Michael T.,
Koong Albert C.,
Yang George P.
Publication year - 2017
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12603
Subject(s) - xbp1 , endoplasmic reticulum , keloid , hypertrophic scar , extracellular matrix , wound healing , microbiology and biotechnology , chemistry , unfolded protein response , rna splicing , biology , biochemistry , pathology , immunology , medicine , anatomy , gene , rna
Wound healing is characterized by the production of large amounts of protein necessary to replace lost cellular mass and extracellular matrix. The unfolded protein response (UPR) is an important adaptive cellular response to increased protein synthesis. One of the main components of the UPR is IRE1, an endoplasmic reticulum transmembrane protein with endonuclease activity that produces the activated form of the transcription factor XBP1. Using luciferase reporter mice for Xbp1 splicing, we showed that IRE1 was up‐regulated during excisional wound healing at the time in wound healing consistent with that of the proliferative phase, when the majority of protein synthesis for cellular proliferation and matrix deposition occurs. Furthermore, using a small molecule inhibitor of IRE1 we demonstrated that inhibition of IRE1 led to decreased scar formation in treated mice. Results were recapitulated in a hypertrophic scar mouse model. These data help provide a cellular pathway to target in the treatment of hypertrophic scarring and keloid disorders.