2. Academic Validation
  3. Inhibition of YAP1 activity ameliorates acute lung injury through promotion of M2 macrophage polarization

Inhibition of YAP1 activity ameliorates acute lung injury through promotion of M2 macrophage polarization

  • MedComm (2020). 2023 Jun 5;4(3):e293. doi: 10.1002/mco2.293.
Lu Liang 1,  Wenyan Xu 1,  Ao Shen 1,  Xiaomei Fu 1,  Huiyu Cen 1,  Siran Wang 2,  Zhongxiao Lin 1 3,  Lingmin Zhang 1,  Fangyu Lin 4,  Xin Zhang 3,  Na Zhou 3,  Jishuo Chang 1,  Zhe-Sheng Chen 5,  Chuwen Li 1,  Xiyong Yu 1
Affiliations

Affiliations

  • 1 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology The State & NMPA Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences & The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou China.
  • 2 Department of Preventive Dentistry Affiliated Stomatology Hospital of Guangzhou Medical University Guangdong Engineering Research Center of Oral Restoration and Reconstruction Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine Guangzhou China.
  • 3 State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology Avenida Wailong Taipa Macau China.
  • 4 Department of Ophthalmology B5500 Clinic B 1365B Clifton Road NE Emory University Atlanta Georgia USA.
  • 5 Department of Pharmaceutical Sciences Institute for Biotechnology College of Pharmacy and Health Sciences St. John's University Queens New York USA.
PMID: 37287755 DOI: 10.1002/mco2.293
Abstract

The balance of M1/M2 macrophage polarization plays an important role in regulating inflammation during acute lung injury (ALI). Yes-associated protein (YAP1) is a key protein in the Hippo-YAP1 signaling pathway and is involved in macrophage polarization. We aimed to determine the role of YAP1 in pulmonary inflammation following ALI and regulation of M1/M2 polarization. Pulmonary inflammation and injury with upregulation of YAP1 were observed in lipopolysaccharide (LPS)-induced ALI. The YAP1 inhibitor, verteporfin, attenuated pulmonary inflammation and improved lung function in ALI mice. Moreover, verteporfin promoted M2 polarization and inhibited M1 polarization in the lung tissues of ALI mice and LPS-treated bone marrow-derived macrophages (BMMs). Additionally, siRNA knockdown confirmed that silencing Yap1 decreased chemokine ligand 2 (CCL2) expression and promoted M2 polarization, whereas silencing large tumor suppressor 1 (Lats1) increased CCL2 expression and induced M1 polarization in LPS-treated BMMs. To investigate the role of inflammatory macrophages in ALI mice, we performed single-cell RNA sequencing of macrophages isolated from the lungs. Thus, verteporfin could activate the immune-inflammatory response, promote the potential of M2 macrophages, and alleviate LPS-induced ALI. Our results reveal a novel mechanism where YAP1-mediated M2 polarization alleviates ALI. Therefore, inhibition of YAP1 may be a target for the treatment of ALI.

Keywords

Yes‐associated protein 1; acute lung injury; macrophage polarization; pulmonary inflammation.

Figures
Products