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纤维蛋白溶解系统成分的协调表达对肺泡上皮细胞凋亡和肺纤维化的调节。

Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system.

机构信息

Texas Lung Injury Institute, Department of Medicine, The University of Texas Health Science Center, Tyler, Texas 75708, USA.

出版信息

Am J Physiol Lung Cell Mol Physiol. 2012 Mar 1;302(5):L463-73. doi: 10.1152/ajplung.00099.2011. Epub 2011 Dec 2.

Abstract

Alveolar type II (ATII) cell apoptosis and depressed fibrinolysis that promotes alveolar fibrin deposition are associated with acute lung injury (ALI) and the development of pulmonary fibrosis (PF). We therefore sought to determine whether p53-mediated inhibition of urokinase-type plasminogen activator (uPA) and induction of plasminogen activator inhibitor-1 (PAI-1) contribute to ATII cell apoptosis that precedes the development of PF. We also sought to determine whether caveolin-1 scaffolding domain peptide (CSP) reverses these changes to protect against ALI and PF. Tissues as well as isolated ATII cells from the lungs of wild-type (WT) mice with BLM injury show increased apoptosis, p53, and PAI-1, and reciprocal suppression of uPA and uPA receptor (uPAR) protein expression. Treatment of WT mice with CSP reverses these effects and protects ATII cells against bleomycin (BLM)-induced apoptosis whereas CSP fails to attenuate ATII cell apoptosis or decrease p53 or PAI-1 in uPA-deficient mice. These mice demonstrate more severe PF. Thus p53 is increased and inhibits expression of uPA and uPAR while increasing PAI-1, changes that promote ATII cell apoptosis in mice with BLM-induced ALI. We show that CSP, an intervention targeting this pathway, protects the lung epithelium from apoptosis and prevents PF in BLM-induced lung injury via uPA-mediated inhibition of p53 and PAI-1.

摘要

肺泡 II 型 (ATII) 细胞凋亡和纤维蛋白溶解功能降低导致肺泡内纤维蛋白沉积与急性肺损伤 (ALI) 和肺纤维化 (PF) 的发生有关。因此,我们试图确定 p53 介导的尿激酶型纤溶酶原激活物 (uPA) 抑制和纤溶酶原激活物抑制剂-1 (PAI-1) 的诱导是否有助于 ALI 发生之前的 ATII 细胞凋亡。我们还试图确定 caveolin-1 支架结构域肽 (CSP) 是否可以逆转这些变化,从而预防 ALI 和 PF。BLM 损伤的野生型 (WT) 小鼠的肺组织和分离的 ATII 细胞显示凋亡增加、p53 和 PAI-1 增加,uPA 和 uPA 受体 (uPAR) 蛋白表达受到相反抑制。用 CSP 处理 WT 小鼠可逆转这些效应,并可保护 ATII 细胞免受博来霉素 (BLM) 诱导的凋亡,而 CSP 不能减轻 uPA 缺陷型小鼠的 ATII 细胞凋亡或降低 p53 或 PAI-1。这些小鼠表现出更严重的 PF。因此,p53 增加并抑制 uPA 和 uPAR 的表达,同时增加 PAI-1,这些变化促进了 BLM 诱导的 ALI 小鼠的 ATII 细胞凋亡。我们表明,CSP 通过 uPA 介导的 p53 和 PAI-1 抑制,靶向该途径的干预措施可保护肺上皮细胞免于凋亡并预防 BLM 诱导的肺损伤中的 PF。

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Post-transcriptional regulation of urokinase-type plasminogen activator receptor expression in lipopolysaccharide-induced acute lung injury.
Am J Respir Crit Care Med. 2009 Feb 15;179(4):288-98. doi: 10.1164/rccm.200712-1787OC. Epub 2008 Nov 21.
3
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4
Inchoate CD8+ T cell responses in neonatal mice permit influenza-induced persistent pulmonary dysfunction.
J Immunol. 2008 Sep 1;181(5):3486-94. doi: 10.4049/jimmunol.181.5.3486.
5
Regulation of plasminogen activator inhibitor-1 expression by tumor suppressor protein p53.
J Biol Chem. 2008 Jul 11;283(28):19570-80. doi: 10.1074/jbc.M710268200. Epub 2008 May 9.
6
Urokinase expression by tumor suppressor protein p53: a novel role in mRNA turnover.
Am J Respir Cell Mol Biol. 2008 Sep;39(3):364-72. doi: 10.1165/rcmb.2007-0406OC. Epub 2008 Apr 3.
7
Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo.
Am J Physiol Lung Cell Mol Physiol. 2008 May;294(5):L843-61. doi: 10.1152/ajplung.00295.2007. Epub 2008 Jan 18.
8
Plasminogen activation induced pericellular fibronectin proteolysis promotes fibroblast apoptosis.
Am J Respir Cell Mol Biol. 2008 Jan;38(1):78-87. doi: 10.1165/rcmb.2007-0174OC. Epub 2007 Jul 26.
9
Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis.
Am J Respir Crit Care Med. 2007 Dec 15;176(12):1261-8. doi: 10.1164/rccm.200610-1491OC. Epub 2007 Jul 19.

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