Khan、Muzamil Majid和Poeckel、Daniel和Halavatyi、Aliaksandr和Zukowska-Kasprzyk、Joanna和Stein、Frank和Vappiani、Johanna和Sevin、Daniel C.和Tischer、Christian和Zinn、Nico和Eley、Jessica D和Gudmann、Natasja St . hr和Muley、Thomas和Winter、Hauke和Fisher、Andrew J and Nanthakumar, Carmel B. and Bergamini, Carmel B. and Pepperkok, Rainer}， title = {An integrated multiomand quantitative label-free microsbased approach to study pro-fibrotic signaling in vitro human precision cut lung slices}，定位id = {2000221}， year = {2020}， doi = {10.1183/13993003.00221-2020}，纤维化可影响任何器官，导致188bet官网地址组织结构和功能的丧失，经常造成危及生命的后果。病理上，纤维化的特征是结缔组织扩张，这是由于细胞外基质蛋白(ECM)的过度沉积，包括胶原纤维形式。发现纤维化治疗方法的一个重要限制是，可用合适的人类模型和技术来量化成熟纤维胶原沉积，尽可能接近人类生理条件。在这里，我们广泛描述了体外培养的人肺组织来源的精确切割肺切片模型(hPCLS)，使用无标记二次谐波(SHG)光镜量化纤维胶原沉积，并使用基于质谱的技术获得hPCLS在体外培养的蛋白质组学和代谢组学指纹图谱。我们证明，在离体培养中，hPCLS与间充质细胞、上皮细胞、内皮细胞和免疫细胞类型均可存活至少2周，并具有代谢活性。hpcls条件下的上清分析显示，在TGF{\ss}1刺激下，肺纤维化相关ECM蛋白有强烈的诱导作用。ECM蛋白的上调并没有转化为纤维胶原蛋白沉积的增加。为了支持这一观察，我们发现在我们的体外培养的hPCLS中存在一种前ecm降解活性，金属蛋白酶抑制剂抑制这种活性，导致在TGF{\ss}1刺激下胶原沉积增加。这些数据表明，测量可溶性前纤维化标记物和基于shg的纤维胶原定量分析的综合方法是研究前纤维化信号和检测抗纤维化药物的有价值的工具。脚注本手稿最近已被接受发表在欧洲呼吸杂志。 It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Khan has nothing to disclose.Conflict of interest: Dr. Poeckel has nothing to disclose.Conflict of interest: Dr. Halavatyi has nothing to disclose.Conflict of interest: Mrs. Kasprzyk has nothing to disclose.Conflict of interest: Dr. Stein has nothing to disclose.Conflict of interest: Dr. Vappiani has nothing to disclose.Conflict of interest: Dr. Sevin has nothing to disclose.Conflict of interest: Dr. Tischer has nothing to disclose.Conflict of interest: Dr. Zinn has nothing to disclose.Conflict of interest: Dr. Eley has nothing to disclose.Conflict of interest: Dr. Gudmann has nothing to disclose.Conflict of interest: Dr. Muley has nothing to disclose.Conflict of interest: Dr. Winter has nothing to disclose.Conflict of interest: Dr. Fisher reports grants from GlaxoSmithKline, during the conduct of the study; grants from Pfizer, grants from Nuformix, grants from Genentech, outside the submitted work;.Conflict of interest: Dr. Nanthakumar has nothing to disclose.Conflict of interest: Dr. Bergamini has nothing to disclose.Conflict of interest: Dr. Pepperkok has nothing to disclose.}, issn = {0903-1936}, URL = {//www.qdcxjkg.com/content/early/2020/12/17/13993003.00221-2020}, eprint = {//www.qdcxjkg.com/content/early/2020/12/17/13993003.00221-2020.full.pdf}, journal = {European Respiratory Journal} }