The expression and function of Gpnmb in lymphatic endothelial cells

Trinity A Kronk; Ernesto Solorzano; Gabrielle T Robinson; Joshua Castor; Hope C Ball; Fayez F Safadi

doi:10.1016/j.gene.2024.148993

The expression and function of Gpnmb in lymphatic endothelial cells

Gene. 2024 Oct 8:148993. doi: 10.1016/j.gene.2024.148993. Online ahead of print.

Authors

Trinity A Kronk¹, Ernesto Solorzano², Gabrielle T Robinson³, Joshua Castor⁴, Hope C Ball⁵, Fayez F Safadi⁶

Affiliations

¹ Department of Anatomy and Neurobiology, College of Medicine, Northeast Ohio Medical University, OH, USA; Basic and Translational Biomedicine, College of Graduate Studies, Northeast Ohio Medical University, OH, USA; Musculoskeletal Research Group, Northeast Ohio Medical University, Rootstown, OH, USA; Department of Orthopaedics, Akron Children's Hospital, OH, USA; University Hospitals, Cleveland, OH, USA.
² Department of Anatomy and Neurobiology, College of Medicine, Northeast Ohio Medical University, OH, USA; Basic and Translational Biomedicine, College of Graduate Studies, Northeast Ohio Medical University, OH, USA; Musculoskeletal Research Group, Northeast Ohio Medical University, Rootstown, OH, USA.
³ Department of Anatomy and Neurobiology, College of Medicine, Northeast Ohio Medical University, OH, USA; Basic and Translational Biomedicine, College of Graduate Studies, Northeast Ohio Medical University, OH, USA; Musculoskeletal Research Group, Northeast Ohio Medical University, Rootstown, OH, USA; University Hospitals, Cleveland, OH, USA.
⁴ Department of Anatomy and Neurobiology, College of Medicine, Northeast Ohio Medical University, OH, USA; Foundations of Medicine, College of Graduate Studies, Northeast Ohio Medical University, OH, USA.
⁵ Rebecca D. Considine Research Institute, Akron Children's Hospital, OH, USA.
⁶ Department of Anatomy and Neurobiology, College of Medicine, Northeast Ohio Medical University, OH, USA; Basic and Translational Biomedicine, College of Graduate Studies, Northeast Ohio Medical University, OH, USA; Musculoskeletal Research Group, Northeast Ohio Medical University, Rootstown, OH, USA; University Hospitals, Cleveland, OH, USA; Rebecca D. Considine Research Institute, Akron Children's Hospital, OH, USA; School of Biomedical Sciences, Kent State University, Kent, OH, USA. Electronic address: fsafadi@neomed.edu.

PMID: 39389329
DOI: 10.1016/j.gene.2024.148993

Abstract

The lymphatic system functions in fluid homeostasis, lipid absorption and the modulation of the immune response. The role of Gpnmb (osteoactivin), an established osteoinductive molecule with newly identified anti-inflammatory properties, has not been studied in lymphangiogenesis. Here, we demonstrate that Gpnmb increases lymphatic endothelial cell (LEC) migration and lymphangiogenesis marker gene expression in vitro by enhancing pro-autophagic gene expression, while no changes were observed in cell proliferation or viability. In addition, cellular spreading and cytoskeletal reorganization was not altered following Gpnmb treatment. We show that systemic Gpnmb overexpression in vivo leads to increases in lymphatic tubule number per area. Overall, data presented in this study suggest Gpnmb is a positive modulator of lymphangiogenesis.

Keywords: Autophagy; Cell migration; Gpnmb; Lymphatic endothelial cells; Osteoactivin.