The local wound environment is a key determinant of the outcome of TGFβ signaling on the fibrotic response of CD44(+) leader cells in an ex vivo post-cataract-surgery model.
The local wound environment is a key determinant of the outcome of TGFβ signaling on the fibrotic response of CD44(+) leader cells in an ex vivo post-cataract-surgery model.
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DOI：
10.1016/j.exer.2021.108829
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发表时间：
2021-12
影响因子：
3.4
通讯作者：
Walker JL
中科院分区：
文献类型：
--
作者：
Basta MD;Paulson H;Walker JL
细胞因子转化生长因子β（TGFβ）在调节伤口愈合的正常和病理反应中发挥作用，但它如何在伤口环境中从促修复功能转变为促纤维化功能仍不清楚。使用模拟晶状体纤维化疾病后囊混浊 (PCO) 的临床相关离体白内障手术后模型，我们研究了两种不同的伤口环境对形成 TGFβ 介导的富含 CD44+ 波形蛋白的前导细胞的损伤反应的影响。在伤口的前缘，该细胞群对刚性伤口环境的大量纤维化反应需要内源性 TGFβ。然而，在内源性基底膜伤口环境中，TGFβ对于前导细胞在伤口愈合中的作用是可有可无的，其中修复是在没有主要纤维化结果的情况下发生的。这些不同环境中前导细胞功能之间的差异在于其细胞表面表达潜在的 TGFβ 激活剂 αvβ3 整合素。当 CD44+ 细胞群定位于刚性伤口环境的前缘时，该受体仅定位于该 CD44+ 细胞群。提供外源性 TGFβ 来绕过前导细胞在不同环境中维持 TGFβ 激活的能力的任何差异，揭示了它们在基底膜伤口环境中诱导促纤维化反应的固有能力。此外，刚性伤口环境中的前导细胞暴露于TGFβ会导致纤维化反应加速，包括原胶原+细胞和α平滑肌肌动蛋白（αSMA）+肌成纤维细胞的早期出现以及纤维化基质产生的增加。总的来说，这些发现显示了局部伤口环境对 TGFβ 诱导的纤维化反应的程度和严重性的影响，这对于了解白内障手术伤口引起的晶状体纤维化疾病 PCO 的发展具有重要意义。
The cytokine transforming growth factor beta (TGFβ) has a role in regulating the normal and pathological response to wound healing, yet how it shifts from a pro-repair to a pro-fibrotic function within the wound environment is still unclear. Using a clinically relevant ex vivo post-cataract surgery model that mimics the lens fibrotic disease posterior capsule opacification (PCO), we investigated the influence of two distinct wound environments on shaping the TGFβ-mediated injury response of CD44+ vimentin-rich leader cells. At the leading edge of the wound, the substantial fibrotic response of this cell population to a rigid wound environment required endogenous TGFβ. However, TGFβ was dispensable for the role of leader cells in wound healing in the endogenous basement membrane wound environment, where repair occurs in the absence of a major fibrotic outcome. A difference between leader cell function in these distinct environments was their cell surface expression of the latent TGFβ activator, αvβ3 integrin. This receptor localized exclusively to this CD44+ cell population when they localize to the leading edge of the rigid wound environment. Providing exogenous TGFβ to bypass any differences in the ability of the leader cells to sustain activation of TGFβ in different environments revealed their inherent ability to induce pro-fibrotic reactions on the basement membrane wound environment. Furthermore, exposure of the leader cells in the rigid wound environment to TGFβ led to an accelerated fibrotic response including the earlier appearance of pro-collagen+ cells and alpha smooth muscle actin (αSMA)+ myofibroblasts and increased fibrotic matrix production. Collectively, these findings show the influence of the local wound environment on the extent and severity of TGFβ-induced fibrotic responses, which has important implications for understanding the development of the lens fibrotic disease PCO in response to cataract surgery wounding.
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DOI：
10.3109/08977194.2011.595714
发表时间：
2011-10
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Biernacka A;Dobaczewski M;Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
4
作者：
Acharya, Pinak S.;Majumdar, Sonali;Pure, Ellen
通讯作者：
Pure, Ellen
DOI：
10.3410/b2-78
发表时间：
2010-11-11
期刊：
F1000 biology reports
影响因子：
--
作者：
Hinz B;Gabbiani G
通讯作者：
Gabbiani G
影响因子：
7.2
作者：
Hynes, Richard O.;Naba, Alexandra
通讯作者：
Naba, Alexandra
影响因子：
5.7
作者：
Korol, Anna;Taiyab, Aftab;West-Mays, Judith A.
通讯作者：
West-Mays, Judith A.