The resolution of lymphedema by interstitial flow in the mouse tail skin.
The resolution of lymphedema by interstitial flow in the mouse tail skin.
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通过小鼠尾部皮肤的间质流动解决淋巴水肿。
DOI：
10.1152/ajpheart.00900.2007
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Goldman,Jeremy
中科院分区：
文献类型：
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作者：
Uzarski,Joseph;Drelles,MeganB;Gibbs,SaraE;Ongstad,EmilyL;Goral,JulieC;McKeown,KatherineK;Raehl,AlishaM;Roberts,MelissaA;Pytowski,Bronislaw;Smith,MartynR;Goldman,Jeremy
淋巴管生成被认为是在继发性淋巴水肿期间增加液体排出的一种有前景的方法。然而，淋巴管进入功能性毛细血管的组织可能依赖于间质流动(IF)。本研究旨在确定淋巴管生成对淋巴水肿消退的重要性。我们制造了一种淋巴阻塞，导致小鼠尾巴皮肤出现淋巴水肿。发生在梗阻上的相对无疤痕的皮肤再生可以观察到淋巴管生成的进展，并与淋巴水肿的演变进行比较。通过外源性给予血管内皮生长因子-C(VEGFR-C)或中和VEGFR-3抗体，研究血管内皮生长因子-C(VEGFR-C)/VEGFR-3信号在淋巴水肿消退中的作用。15天后[真皮厚度从74 2±10 5降至5 5 9±14 1μm，95%可信区间(P<0.0 5)]，淋巴管覆盖率(11.6±6.4%，95%可信区间为9.6±6.2%，P>；0.5 0)。阻断VEGFR-3信号通路并不能抑制第25天的淋巴水肿消退(抑制VEGFR-3后真皮厚度为462±127μm，95%顺式时为502±87μm)或抑制IF，尽管阻断VEGFR-3信号可阻止淋巴管生成(95%顺式时淋巴管覆盖率降至0.2±0.7%，顺式为8.7±7.3%，P<；0.005)。第二个小鼠尾巴淋巴水肿模型被用来研究血管内皮生长因子-C增加疤痕液体排出的能力。我们发现，VEGFR-3的中和和VEGF-C的应用都不会影响超过25天的皮肤肿胀过程。这些发现表明，小鼠尾部皮肤淋巴水肿的缓解可能更多地依赖于细胞外基质跨梗阻的再生，而不是淋巴管的再生。
Lymphangiogenesis is considered a promising approach for increasing fluid drainage during secondary lymphedema. However, organization of lymphatics into functional capillaries may be dependent upon interstitial flow (IF). The present study was undertaken to determine the importance of lymphangiogenesis for lymphedema resolution. We created a lymphatic obstruction that produces lymphedema in mouse tail skin. The relatively scar-free skin regeneration that occurred across the obstruction allowed the progression of lymphangiogenesis to be observed and compared with the evolution of lymphedema. The role of vascular endothelial growth factor-C (VEGF-C)/VEGF receptor (VEGFR)-3 signaling in lymphedema resolution was investigated by exogenous administration of VEGF-C or neutralizing antibodies against VEGFR-3. VEGF-C protein improved lymphedema at 15 days [reducing dermal thickness from 742 ± 105 to 559 ± 141 μm with 95% confidence intervals (CIs),P< 0.05] without increasing lymphatic capillary coverage (11.6 ± 6.4% following VEGF-C treatment relative to 9.6 ± 6.2% with 95% CIs,P> 0.50). Blocking VEGFR-3 signaling did not inhibit lymphedema resolution at 25 days (dermal thickness of 462 ± 127 μm following VEGFR-3 inhibition relative to 502 ± 87 μm with 95% CIs) or inhibit IF, although VEGFR-3 blocking prevented lymphangiogenesis (reducing lymphatic coverage to 0.2 ± 0.7% relative to 8.7 ± 7.3% with 95% CIs,P< 0.005). A second mouse tail lymphedema model was employed to investigate the ability of VEGF-C to increase fluid drainage across a scar. We found that neither neutralization of VEGFR-3 nor administration of VEGF-C affected the course of skin swelling over 25 days. These findings suggest that resolution of lymphedema in the mouse tail skin may be more dependent upon IF and regeneration of the extracellular matrix across the obstruction than lymphatic capillary regeneration.