Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro
Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro
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DOI：
10.1242/jcs.02605
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发表时间：
2005-10-15
影响因子：
4
通讯作者：
Swartz, MA
中科院分区：
文献类型：
--
作者：
Ng, CP;Hinz, B;Swartz, MA
成纤维细胞分化为收缩性肌成纤维细胞，其特征在于α-平滑肌肌动蛋白（α-SMA）的从头表达，这对于伤口愈合至关重要，并且是组织瘢痕形成和纤维化的标志。这些过程通常发生在炎症事件之后，特别是在皮肤、肺和肝等软组织中。虽然炎性细胞和受损的上皮细胞可以释放转化生长因子β（1）（TGF-β（1）），其在很大程度上介导肌成纤维细胞分化，但炎症和组织再生的生物物理环境，即由于血管通透性过高和/或血管生成而增加的间质流动，也可能起作用。我们证明，低水平的间质（3D）流动会诱导成纤维细胞向肌成纤维细胞的分化以及胶原排列和成纤维细胞增殖，所有这些都是在不存在外源性介质的情况下进行的。这些作用与TGF-β 1诱导有关，并且可以用TGF-β 1阻断抗体消除。此外，α（1）β（1）整联蛋白被认为在对流动的特异性反应中起重要作用，因为其抑制阻止了成纤维细胞分化和随后的胶原排列，但在单独的浮动凝胶测定中并不阻止其收缩凝胶的能力。这项研究表明，通常在纤维化之前的生物物理环境，如肿胀，微血管通透性增加和淋巴引流增加-所有这些都涉及间质液流动-本身可能在纤维化中发挥重要作用。
The differentiation of fibroblasts to contractile myofibroblasts, which is characterized by de novo expression of alpha-smooth muscle actin (alpha-SMA), is crucial for wound healing and a hallmark of tissue scarring and fibrosis. These processes often follow inflammatory events, particularly in soft tissues such as skin, lung and liver. Although inflammatory cells and damaged epithelium can release transforming growth factor beta(1) (TGF-beta(1)), which largely mediates myofibroblast differentiation, the biophysical environment of inflammation and tissue regeneration, namely increased interstitial flow owing to vessel hyperpermeability and/or angiogenesis, may also play a role. We demonstrate that low levels of interstitial (3D) flow induce fibroblast-to-myofibroblast differentiation as well as collagen alignment and fibroblast proliferation, all in the absence of exogenous mediators. These effects were associated with TGF-beta(1) induction, and could be eliminated with TGF-beta(1) blocking antibodies. Furthermore, alpha(1)beta(1) integrin was seen to play an important role in the specific response to flow, as its inhibition prevented fibroblast differentiation and subsequent collagen alignment but did not block their ability to contract the gel in a separate floating gel assay. This study suggests that the biophysical environment that often precedes fibrosis, such as swelling, increased microvascular permeability and increased lymphatic drainage - all which involve interstitial fluid flow - may itself play an important role in fibrogenesis.