Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity

• Published in: Development (Cambridge) Vol. 144; no. 19; pp. 3590 - 3601
• Main Authors: Wang, Yixin, Jin, Yi, Mäe, Maarja Andaloussi, Zhang, Yang, Ortsäter, Henrik, Betsholtz, Christer, Mäkinen, Taija, Jakobsson, Lars
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01.10.2017
• Subjects: Animals; Animals, Newborn; Capillaries; Capillaries - metabolism; Cell Communication; Clonal deletion; Contraction; Dermis - metabolism; Endothelial cells; Endothelial Cells - metabolism; Extracellular matrix; Extracellular Matrix - metabolism; Female; Hindlimb - metabolism; Lymphatic system; Lymphatic vasculature; Lymphatic Vessels - anatomy & histology; Lymphatic Vessels - metabolism; Lymphedema; Male; Mesentery - metabolism; Morphogenesis; Myocytes, Smooth Muscle - metabolism; Organ Size; PDGFB; Platelet-derived growth factor; Platelet-derived growth factor B; Proto-Oncogene Proteins c-sis - metabolism; Rodents; Skin; Smooth muscle; Smooth muscle cell; Morphogenesis; Smooth muscle cell; PDGFB; Lymphatic vasculature; Lymphedema; Contraction
• ISSN: 0950-1991; 1477-9129; 1477-9129
• DOI: 10.1242/dev.147967

Tissue-fluid drains through blind-ended lymphatic capillaries, via smooth muscle cell (SMC)-covered collecting vessels into venous circulation. Both defective SMC recruitment to collecting vessels and ectopic recruitment to lymphatic capillaries are thought to contribute to vessel failure, leading to lymphedema. However, mechanisms controlling lymphatic SMC recruitment and their role in vessel maturation are unknown. Here we demonstrate that platelet-derived growth factor B (PDGFB) regulates lymphatic SMC recruitment in multiple vascular beds. PDGFB is selectively expressed by lymphatic endothelial cells (LECs) of collecting vessels. LEC-specific deletion of Pdgfb prevented SMC recruitment causing dilation and failure of pulsatile contraction of collecting vessels. However, vessel remodelling and identity were unaffected. Unexpectedly, PDGFB overexpression in LECs did not induce SMC recruitment to capillaries. This was explained by the demonstrated requirement of PDGFB extracellular matrix (ECM) retention for lymphatic SMC recruitment, and low presence of PDGFB-binding ECM components around lymphatic capillaries. These results demonstrate a requirement of LEC-autonomous PDGFB expression and retention for SMC recruitment to lymphatic vessels and suggest an ECM-controlled checkpoint preventing SMC investment of capillaries, which is a common feature in lymphedematous skin.