The common YAP activation mediates corneal epithelial regeneration and repair with different-sized wounds

  • NPJ Regen Med. 2021 Mar 26;6(1):16. doi: 10.1038/s41536-021-00126-2.
Yijian Li  1  2 ,  Lingling Ge  3  4 ,  Xia Chen  3  4  5 ,  Yumei Mao  6 ,  Xianliang Gu  3  4 ,  Bangqi Ren  3  4 ,  Yuxiao Zeng  3  4 ,  Min Chen  3  4 ,  Siyu Chen  3  4 ,  Jinhua Liu  3  4 ,  Yuli Yang  7  8 ,  Haiwei Xu  9  10
Affiliations
  • 1. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China. [email protected].
  • 2. Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China. [email protected].
  • 3. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • 4. Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China.
  • 5. Southwest University, Chongqing, China.
  • 6. North Sichuan Medical College, Sichuan, China.
  • 7. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China. [email protected].
  • 8. Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China. [email protected].
  • 9. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China. [email protected].
  • 10. Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China. [email protected].
PMID: 33772031 DOI: 10.1038/s41536-021-00126-2
Abstract

Regeneration/repair after injury can be endowed by adult stem cells (ASCs) or lineage restricted and even terminally differentiated cells. In corneal epithelium, regeneration after a large wound depends on ASCs (limbal epithelial stem cells, LESCs), whereas repair after a small wound is LESCs-independent. Here, using rat corneal epithelial wounds with different sizes, we show that YAP activation promotes the activation and expansion of LESCs after a large wound, as well as the reprogramming of local epithelial cells (repairing epithelial cells) after a small wound, which contributes to LESCs-dependent and -independent wound healing, respectively. Mechanically, we highlight that the reciprocal regulation of YAP activity and the assembly of cell junction and cortical F-actin Cytoskeleton accelerates corneal epithelial healing with different-sized wounds. Together, the common YAP activation and the underlying regulatory mechanism are harnessed by LESCs and lineage-restricted epithelial cells to cope with corneal epithelial wounds with different sizes.

Products