| First Author | Tu CL | Year | 2019 |
| Journal | J Invest Dermatol | Volume | 139 |
| Issue | 4 | Pages | 919-929 |
| PubMed ID | 30404020 | Mgi Jnum | J:309665 |
| Mgi Id | MGI:6759255 | Doi | 10.1016/j.jid.2018.09.033 |
| Citation | Tu CL, et al. (2019) Calcium-Sensing Receptor Regulates Epidermal Intracellular Ca(2+) Signaling and Re-Epithelialization after Wounding. J Invest Dermatol 139(4):919-929 |
| abstractText | Extracellular Ca(2+) (Ca(2+)o) is a crucial regulator of epidermal homeostasis and its receptor, the Ca(2+)-sensing receptor (CaSR), conveys the Ca(2+)o signals to promote keratinocyte adhesion, differentiation, and survival via activation of intracellular Ca(2+) (Ca(2+)i) and E-cadherin-mediated signaling. Here, we took genetic loss-of-function approaches to delineate the functions of CaSR in wound re-epithelialization. Cutaneous injury triggered a robust CaSR expression and a surge of Ca(2+)i in epidermis. CaSR and E-cadherin were co-expressed at the cell-cell membrane between migratory keratinocytes in the nascent epithelial tongues. Blocking the expression of CaSR or E-cadherin in cultured keratinocytes markedly inhibited the wound-induced Ca(2+)i propagation and their ability to migrate collectively. Depleting CaSR also suppressed keratinocyte proliferation by downregulating the E-cadherin/epidermal growth factor receptor/mitogen-activated protein kinase signaling axis. Blunted epidermal Ca(2+)i response to wounding and retarded wound healing were observed in the keratinocyte-specific CaSR knockout ((Epid)Casr(-/-)) mice, whose shortened neo-epithelia exhibited declined E-cadherin expression and diminished keratinocyte proliferation and differentiation. Conversely, stimulating endogenous CaSR with calcimimetic NPS-R568 accelerated wound re-epithelialization through enhancing the epidermal Ca(2+)i signals and E-cadherin membrane expression. These findings demonstrated a critical role for the CaSR in epidermal regeneration and its therapeutic potential for improving skin wound repair. |
