Lymphatic Endothelial-to-Myofibroblast Transition: A Potential New Mechanism Underlying Skin Fibrosis in Systemic...

Area of Science:

• Vascular Biology
• Fibrosis Research
• Immunodermatology

Background:

• Limited understanding of the lymphatic system's role in systemic sclerosis (SSc) pathogenesis.
• Blood vascular endothelial cells' endothelial-to-myofibroblast transition (EndMT) is implicated in SSc skin fibrosis.
• Investigating lymphatic endothelium as a potential source of myofibroblasts via lymphatic EndMT (Ly-EndMT).

Purpose of the Study:

• To investigate the potential of lymphatic endothelial cells to undergo EndMT (Ly-EndMT) in SSc.
• To determine if Ly-EndMT contributes to myofibroblast generation and skin fibrosis in SSc patients.

Main Methods:

• Immunohistochemistry on SSc and healthy skin using LYVE-1 and α-SMA markers.
• In vitro culture of human dermal lymphatic microvascular endothelial cells (HdLy-MVECs).
• Stimulation of HdLy-MVECs with TGFβ1 or SSc patient serum, followed by molecular and functional assays.

Main Results:

• Lymphatic endothelial cells coexpressing LYVE-1 and α-SMA (intermediate Ly-EndMT) were found exclusively in SSc fibrotic skin.
• HdLy-MVECs cultured with SSc serum or TGFβ1 exhibited a myofibroblast phenotype.
• Cultured cells showed reduced lymphatic markers and increased myofibroblast markers, with enhanced contractile ability.

Conclusions:

• Lymphatic endothelial cells can undergo Ly-EndMT, acquiring a myofibroblast phenotype.
• Ly-EndMT may represent a novel mechanism in SSc pathogenesis, linking lymphatic dysfunction to skin fibrosis.
• This process offers a potential new target for SSc therapies.