Andonegui Graciela, Krein Peter M, Mowat Connie, Brisebois Ronald, Doig Christopher, Green Francis H Y, Léger Caroline, Winston Brent W
Department of Critical Care Medicine, Faculty of Medicine, University of Calgary Health Research Innovation Center, Calgary, Alberta, Canada Immunology Research Group, Faculty of Medicine, University of Calgary Health Research Innovation Center, Calgary, Alberta, Canada.
Immunology Research Group, Faculty of Medicine, University of Calgary Health Research Innovation Center, Calgary, Alberta, Canada Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary Health Research Innovation Center, Calgary, Alberta, Canada.
Physiol Rep. 2014 Nov 3;2(11). doi: 10.14814/phy2.12197. Print 2014 Nov 1.
Insulin-Like Growth Factor I (IGF-I) has been identified in the lungs of individuals with fibrotic lung diseases. In a previous retrospective study, we showed enhanced IGF-I immunoreactivity in individuals with fibroproliferative acute respiratory distress syndrome (FP-ARDS), but we were unable to determine if this correlation was causative. This study was undertaken to prospectively investigate whether IGF-I expression correlated with the fibroproliferative process and whether IGF-I was induced and made in the lungs. We measured IGF-I and procollagen III peptide (PCP-III) in the epithelial lining fluid (ELF) from controls, early ALI/ARDS patients and FP-ARDS patients. We also measured IGF-I mRNA and immunoreactivity from controls and FP-ARDS patient lung biopsies. We determined the level of lung permeability by measuring albumin and urea levels in ELF and serum. Our data show that IGF-I is significantly increased in the ELF in FP-ARDS patients. A significant correlation between IGF-I and PCP-III in the ELF of FP-ARDS patients is found. IGF-I mRNA is elevated in the FP-ARDS lung biopsies. Our data suggest that IGF-I found in the lungs of FP-ARDS patients results from both increased lung permeability and local production of IGF-I. The role of IGF-I in the fibroproliferative process in the lungs has recently been confirmed in an animal model of lung fibroproliferation. This study importantly suggest that IGF-I protein is made in the lungs of FP-ARDS patients and correlates with increased levels of ELF PCP-III, implicating a role for IGF-I in the fibroproliferative process in humans.
胰岛素样生长因子I（IGF-I）已在患有肺纤维化疾病的个体的肺部中被发现。在先前的一项回顾性研究中，我们发现纤维增生性急性呼吸窘迫综合征（FP-ARDS）患者的IGF-I免疫反应性增强，但我们无法确定这种相关性是否具有因果关系。本研究旨在前瞻性地调查IGF-I表达是否与纤维增生过程相关，以及IGF-I是否在肺部被诱导产生。我们测量了对照组、早期急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）患者和FP-ARDS患者上皮衬液（ELF）中的IGF-I和前胶原III肽（PCP-III）。我们还测量了对照组和FP-ARDS患者肺活检组织中的IGF-I mRNA和免疫反应性。我们通过测量ELF和血清中的白蛋白和尿素水平来确定肺通透性水平。我们的数据表明，FP-ARDS患者的ELF中IGF-I显著增加。在FP-ARDS患者的ELF中发现IGF-I与PCP-III之间存在显著相关性。FP-ARDS肺活检组织中的IGF-I mRNA升高。我们的数据表明，FP-ARDS患者肺部中的IGF-I是肺通透性增加和IGF-I局部产生共同作用的结果。最近在肺纤维增生动物模型中证实了IGF-I在肺部纤维增生过程中的作用。这项研究重要地表明，FP-ARDS患者的肺部产生IGF-I蛋白，并且与ELF中PCP-III水平升高相关，这表明IGF-I在人类纤维增生过程中发挥作用。
