Indirubin-pregnane X receptor-JNK axis accelerates skin wound healing

Yuka Tanaka, Hiroshi Uchi, Takamichi Ito, Masutaka Furue

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Indirubin is a potent anti-inflammatory phytochemical derived from indigo naturalis. It is also endogenously produced in the intestine and detected in the circulation in mammals. Indirubin exerts its biological functions via two xenobiotic receptor systems: aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR); however, its effects on wound healing remain elusive. To investigate whether indirubin promotes wound healing, we utilized an in vitro scratch injury assay and in vivo full-thickness mouse skin ulcer model and assessed wound closure. Indirubin significantly accelerated wound closure in both the scratch assay and the skin ulcer model. Using inhibitors of cell proliferation or migration, indirubin was found to upregulate the migratory but not the proliferative capacity of keratinocytes. Activation of AHR/PXR by indirubin was confirmed by their nuclear translocation and subsequent upregulation of CYP1A1 (AHR), or UGT1A1 mRNA (PXR) and also by luciferase reporter assay (PXR). Although both AHR and PXR were activated by indirubin, its pro-migratory capacity was canceled by PXR inhibition but not by AHR inhibition and was dependent on the JNK pathway. Moreover, activated PXR was detected in the nuclei of re-epithelialized keratinocytes in human skin ulcers. In conclusion, this study shows that the indirubin-PXR-JNK pathway promotes skin wound healing.

Original languageEnglish
Article number18174
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

All Science Journal Classification (ASJC) codes

  • General

Fingerprint

Dive into the research topics of 'Indirubin-pregnane X receptor-JNK axis accelerates skin wound healing'. Together they form a unique fingerprint.

Cite this