Cleaved cytokeratin-18 is a mechanistically informative biomarker in idiopathic pulmonary fibrosis.
Cleaved cytokeratin-18 is a mechanistically informative biomarker in idiopathic pulmonary fibrosis.
复制标题
DOI：
10.1186/1465-9921-13-105
复制
发表时间：
2012-11-20
影响因子：
5.8
通讯作者：
Wolters PJ
中科院分区：
文献类型：
--
作者：
Cha SI;Ryerson CJ;Lee JS;Kukreja J;Barry SS;Jones KD;Elicker BM;Kim DS;Papa FR;Collard HR;Wolters PJ
内质网应激导致未折叠蛋白反应(UPR)的激活和肺泡上皮细胞(AEC)的凋亡可能在特发性肺纤维化(IPF)的发病机制中起一定作用。我们的目的是确定循环caspase裂解的细胞角蛋白-18(CCK-18)是否是IPF中AEC凋亡的标志，明确CCK-18与UPR激活的关系，并评估其作为诊断生物标志物的价值。用特异性结合CCK-18的抗体(M30)对IPF和正常肺组织进行染色。体外培养的AECs暴露于thapsigargin诱导的内质网应激，检测UPR和CCK-18标志物之间的关系。测定IPF、过敏性肺炎(HP)、非特异性间质性肺炎(NSIP)患者和正常对照组血清CCK-18水平。CCK-18免疫反应阳性细胞在IPF肺AECs中呈阳性表达，而在正常对照组中未见表达。在IPF II型AEC中，UPR(磷酸化的IRE-1XBP-1和剪接的α-1)的表达高于正常II型AEC。在thapsigargin诱导的内质网应激后，磷酸化的IRE-1α和CCK-18表达增加。血清CCK-18水平可区分IPF患者和正常对照组。血清CCK-18与疾病严重程度或预后无关。CCK-18可能是IPF患者AEC凋亡和UPR活化的标志物。循环CCK-18水平在IPF患者中升高，CCK-18可能是一个有用的诊断生物标志物。
Stress of the endoplasmic reticulum (ER) leading to activation of the unfolded protein response (UPR) and alveolar epithelial cell (AEC) apoptosis may play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our objectives were to determine whether circulating caspase-cleaved cytokeratin-18 (cCK-18) is a marker of AEC apoptosis in IPF, define the relationship of cCK-18 with activation of the UPR, and assess its utility as a diagnostic biomarker. IPF and normal lung tissues were stained with the antibody (M30) that specifically binds cCK-18. The relationship between markers of the UPR and cCK-18 was determined in AECs exposed in vitro to thapsigargin to induce ER stress. cCK-18 was measured in serum from subjects with IPF, hypersensitivity pneumonitis (HP), nonspecific interstitial pneumonia (NSIP), and control subjects. cCK-18 immunoreactivity was present in AECs of IPF lung, but not in control subjects. Markers of the UPR (phosphorylated IRE-1α and spliced XBP-1) were more highly expressed in IPF type II AECs than in normal type II AECs. Phosphorylated IRE-1α and cCK-18 increased following thapsigargin-induced ER stress. Serum cCK-18 level distinguished IPF from diseased and control subjects. Serum cCK-18 was not associated with disease severity or outcome. cCK-18 may be a marker of AEC apoptosis and UPR activation in patients with IPF. Circulating levels of cCK-18 are increased in patients with IPF and cCK-18 may be a useful diagnostic biomarker.
登录
查看更多内容
影响因子：
4.4
作者：
Hagimoto, N;Kuwano, K;Hara, N
通讯作者：
Hara, N
DOI：
10.1165/rcmb.2003-0078oc
发表时间：
2003-12-01
影响因子：
6.4
作者：
Atamas, SP;Luzina, IG;White, B
通讯作者：
White, B
DOI：
10.1164/rccm.200509-1518oc
发表时间：
2006-04-01
影响因子：
24.7
作者：
Prasse, A;Pechkovsky, DV;Zissel, G
通讯作者：
Zissel, G
影响因子：
--
作者：
Prasse, Antje;Pechkovsky, Dmitri V.;Mueller-Quernheirn, Joachim
通讯作者：
Mueller-Quernheirn, Joachim
影响因子：
6.9
作者：
Ryerson, Christopher J.;Abbritti, Marta;Collard, Harold R.
通讯作者：
Collard, Harold R.