Hyaluronan and TLR4 promote surfactant-protein-C-positive alveolar progenitor cell renewal and prevent severe pulmonary fibrosis in mice.
Hyaluronan and TLR4 promote surfactant-protein-C-positive alveolar progenitor cell renewal and prevent severe pulmonary fibrosis in mice.
复制标题
DOI：
10.1038/nm.4192
复制
发表时间：
2016-11
期刊：
影响因子：
82.9
通讯作者：
Noble PW
中科院分区：
文献类型：
--
作者：
Liang J;Zhang Y;Xie T;Liu N;Chen H;Geng Y;Kurkciyan A;Mena JM;Stripp BR;Jiang D;Noble PW
肺损伤的成功恢复需要肺泡上皮细胞的修复和再生，以恢复肺内气体交换区域的完整性并保持器官功能。肺泡上皮的不适当再生通常与严重的肺纤维化有关，后者涉及成纤维细胞的募集和活化以及基质积累。2型肺泡上皮细胞（AEC 2）是成人肺中的干细胞，有助于肺修复过程。调节AEC 2细胞更新的机制尚不完全清楚。我们提供的证据表明，先天免疫受体Toll样受体4（TLR4）和细胞外基质糖胺聚糖透明质酸（HA）的表达对AEC 2更新，肺损伤修复和限制纤维化的程度是重要的。在表面活性蛋白C阳性的AEC 2中，TLR4或HA合酶2的缺失导致更新能力受损、严重的纤维化和死亡率。此外，来自严重肺纤维化患者的AEC 2具有减少的细胞表面HA和受损的更新能力，表明HA和TLR4是肺干细胞更新的关键贡献者，并且严重肺纤维化是远端上皮干细胞衰竭的结果。
Successful recovery from lung injury requires the repair and regeneration of alveolar epithelial cells in order to restore the integrity of gas exchanging regions within the lung and preserve organ function. Improper regeneration of the alveolar epithelium is often associated with severe pulmonary fibrosis, the latter of which involves the recruitment and activation of fibroblasts, as well as matrix accumulation. Type 2 alveolar epithelial cells (AEC2s) are stem cells in the adult lung that contribute to the lung repair process. The mechanisms that regulate AEC2 cell renewal are incompletely understood. We provide evidence that expression of the innate immune receptor Toll like receptor 4 (TLR4) and the extracellular matrix glycosaminoglycan hyaluronan (HA) on AEC2s are important for AEC2 renewal, repair of lung injury, and limiting the extent of fibrosis. Either deletion of TLR4 or HA synthase 2 in surfactant protein-C-positive AEC2s leads to impaired renewal capacity, severe fibrosis and mortality. Furthermore, AEC2s from patients with severe pulmonary fibrosis have reduced cell surface HA and impaired renewal capacity, suggesting that HA and TLR4 are key contributors to lung stem cell renewal and that severe pulmonary fibrosis is the result of distal epithelial stem cell failure.
登录
查看更多内容
DOI：
10.4049/jimmunol.1302470
发表时间：
2014-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Le TT;Karmouty-Quintana H;Melicoff E;Le TT;Weng T;Chen NY;Pedroza M;Zhou Y;Davies J;Philip K;Molina J;Luo F;George AT;Garcia-Morales LJ;Bunge RR;Bruckner BA;Loebe M;Seethamraju H;Agarwal SK;Blackburn MR
通讯作者：
Blackburn MR
影响因子：
82.9
作者：
Cao Z;Lis R;Ginsberg M;Chavez D;Shido K;Rabbany SY;Fong GH;Sakmar TP;Rafii S;Ding BS
通讯作者：
Ding BS
影响因子：
33.6
作者：
Jiang D;Liang J;Noble PW
通讯作者：
Noble PW
DOI：
10.1165/rcmb.2013-0497oc
发表时间：
2015-07-01
影响因子：
6.4
作者：
Liu, Yuru;Kumar, Varsha Suresh;Malik, Asrar B.
通讯作者：
Malik, Asrar B.
DOI：
10.1152/ajplung.00373.2014
发表时间：
2015-04-01
影响因子：
4.9
作者：
Hofer, Christian C.;Woods, Parker S.;Davis, Ian C.
通讯作者：
Davis, Ian C.