CXCR7 Facilitates the Migration and Proliferation of UCMSCs via β-Catenin/TCF4/MDM2 Signal Regulating Notch1 Ubiquitination to Ameliorate Pulmonary Fibrosis in ARDS.

Umbilical cord mesenchymal stem cells (UCMSCs) hold therapeutic potential for acute respiratory distress syndrome (ARDS), but the role of atypical CXC chemokine receptor 7 (CXCR7) in their homing and reparative effects remains unclear. Using a lipopolysaccharide (LPS)-induced ARDS mouse model, we demonstrated that CXCR7 overexpression enhances UCMSC proliferation, migration, and lung repair. Mechanistically, CXCR7 activates the Wnt/β-catenin pathway to upregulate murine double minute (MDM2) transcription, which subsequently ubiquitinates and degrades Notch1, revealing a novel Wnt-Notch crosstalk. These findings highlight CXCR7 as a therapeutic target for ARDS and provide insights into UCMSC-based regenerative strategies.