Urinary Trypsin Inhibitor Attenuates Acute Lung Injury by Improving Endothelial Progenitor Cells Functions

• Published in: Cellular physiology and biochemistry Vol. 36; no. 3; pp. 1059 - 1068
• Main Authors: Guo, Weixin, Li, Zhihong, Xie, Xiaoyun, Qin, Tiehe, Wu, Yan, Li, Zhou, Chai, Jing, Yi, Frank, Tan, Tao, Zhu, Hua, Wang, Shouhong
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01.01.2015
• Subjects: Acute lung injury (ALI); Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - genetics; Acute Lung Injury - pathology; Akt/eNOS; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Capillaries - drug effects; Capillaries - ultrastructure; Endothelial progenitor cells (EPCs); Endothelial Progenitor Cells - drug effects; Endothelial Progenitor Cells - metabolism; Endothelial Progenitor Cells - pathology; Enzyme Activation - drug effects; Eosine Yellowish-(YS); Gene Expression; Glycoproteins - pharmacology; Hematoxylin; Histocytochemistry; Injections, Intravenous; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Lung - blood supply; Lung - drug effects; Lung - pathology; Male; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Oleic Acid; Original Paper; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - agonists; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Rabbits; Signal Transduction; Urinary Trypsin Inhibitor (UTI); Urinary Trypsin Inhibitor (UTI); Endothelial progenitor cells (EPCs); Akt/eNOS; Acute lung injury (ALI)
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000430279

Background: Urinary Trypsin Inhibitor (UTI) is involved in various aspects of tissue repair, regeneration and development. However, the potential role of UTI in protection against acute lung injury (ALI) remains largely unknown. In the present study, we demonstrated that UTI treatment could ameliorate ALI induced by oleic acid (OA) treatment in rabbit model. Methods: Intravenous application of UTI (10000 U/kg/d) significantly improved the pathologies associated with OA-induced ALI. The lungs were stained with hematoxylin and eosin to scored the lung injury. Peripheral blood mononuclear cells were isolated by density gradient centrifugation with Ficoll-Plaque Plus. The proliferation and ability of tube structure formation of EPCs were observed and the level of phosphorylated Akt protein expression and eNOS protein expression were assayed. Results: Consistent with pathological scores, UTI treatment significantly reduced wet/dry ratio of OA injured lungs. A quantification of capillary density revealed that UTI treatment led to about 2 fold increase over uninjured control and about 1.5 fold increase over PBS treatment. The capacity for tube formation of EPCs on ECM gel was significantly reduced in the ALI group and recovered with UTI treatment. Quantification of western blot bands was summarized and showed that UTI treatment activates Akt/eNOS signaling. NO production could contribute to the improvement of EPCs function by UTI treatment. Conclusions: UTI-induced phosphorylation/activation of eNOS and Akt, increases the intracellular level of NO, thereby improving tube formation and proliferation function of EPCs. EPCs function is crucial for re-endothelialization after denuding injuries of arteries.