期刊
DEVELOPMENT
卷 144, 期 19, 页码 3590-3601出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.147967
关键词
Lymphatic vasculature; PDGFB; Contraction; Lymphedema; Morphogenesis; Smooth muscle cell
资金
- William K. Bowes, Jr. Foundation
- Vetenskapsradet [521-2011-3044, 2015-00550, 542-2014-3535]
- Cancerfonden [CAN 2014/855, CAN 2015/0735]
- Cardiovascular Programme
- Strategic Research Programme in Neuroscience at the Karolinska Institutet
- Jeanssons Stiftelser
- Magnus Bergvalls Stiftelse
- Knut och Alice Wallenbergs Stiftelse [2015.0030]
- European Research Council [AdG 294556 Bbbarrier, ERC-2014-CoG-646849]
- Foundation Leducq (Sphingonet)
- Formas [2015-00550] Funding Source: Formas
- Swedish Research Council [2015-00550] Funding Source: Swedish Research Council
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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