Dermal Collagen and Lipid Deposition Correlate with Tissue Swelling and Hydraulic Conductivity in Murine Primary Lymphedema
Dermal Collagen and Lipid Deposition Correlate with Tissue Swelling and Hydraulic Conductivity in Murine Primary Lymphedema
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DOI：
10.2353/ajpath.2010.090733
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发表时间：
2010-03-01
影响因子：
6
通讯作者：
Swartz, Melody A.
中科院分区：
文献类型：
--
作者：
Rutkowski, Joseph M.;Markhus, Carl Erik;Swartz, Melody A.
原发性淋巴水肿是淋巴引流功能障碍的先天性病理，其特征是四肢肿胀、真皮增厚以及皮下组织中液体和脂质积聚。两种原发性淋巴水肿小鼠模型，Chy 小鼠和 K14-VEGFR-3-Ig 小鼠，均缺乏真皮毛细淋巴管，并表现出因 VEGFR-3 信号传导破坏而导致的淋巴水肿表型。在这里，我们表明这两个模型之间水肿组织成分的差异与导水率的巨大差异相关。与各自的野生型对照相比，Chy 小鼠的皮肤具有显着较高水平的胶原蛋白和脂肪，而 K14-VEGFR-3-Ig 小鼠皮肤成分相对正常。从功能上讲，这导致 K14-VEGFR3-Ig 小鼠（而非 Chy）小鼠的皮肤水力传导率大大增加。我们的数据表明，与胶原蛋白和脂质积累增加相关的淋巴水肿抵消了与真皮肿胀相关的水力传导率增加，这反过来又进一步限制了间质运输和肿胀。没有脂质和胶原蛋白的积累，水力传导率会增加，整体肿胀会最小化。这些对原发性淋巴水肿相反的组织反应意味着组织重塑（主要是胶原蛋白和脂肪沉积）可能决定组织肿胀并控制淋巴水肿中的间质运输。 （Am J Pathol 2010，176：1122-1129；DOI：10.2353/ajpath.2010.090733）
Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling-predominantly collagen and fat deposition-may dictate tissue swelling and govern interstitial transport in lymphedema. (Am J Pathol 2010,176:1122-1129; DOI: 10.2353/ajpath.2010.090733)