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

First Author  Wang Y Year  2017
Journal  Development Volume  144
Issue  19 Pages  3590-3601
PubMed ID  28851707 Mgi Jnum  J:245933
Mgi Id  MGI:5917916 Doi  10.1242/dev.147967
Citation  Wang Y, et al. (2017) Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity. Development 144(19):3590-3601
abstractText  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 its 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 the low presence of PDGFB-binding ECM components around lymphatic capillaries. These results demonstrate the requirement of LEC-autonomous PDGFB expression and retention for SMC recruitment to lymphatic vessels, and suggest an ECM-controlled checkpoint that prevents SMC investment of capillaries, which is a common feature in lymphedematous skin.
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