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

Abstract

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.

Blocking CXCR1/2 contributes to amelioration of lipopolysaccharide‐induced sepsis by downregulating substance P

“…ALI is characterized by hypoxemia, rupture of alveolar capillary membranes, and pulmonary edema. Acute respiratory distress syndrome is a severe form of ALI, leading to a mortality rate of up to 40% . It has been shown that overexpression of CXCR4 in neutrophils can cause stem cell death .…”

“…Acute lung injury (ALI) is a fatal syndrome which may cause acute hypoxemic respiratory failure characterized by diffuse alveolar damage, increased permeability of alveolar capillaries, edema, pulmonary inflammation, and alveolar epithelial cell (AEC) apoptosis . Studies have shown that apoptosis of type II AECs may cause damage to epithelial barriers, which further leads to ALI . Lipopolysaccharide (LPS), a component of the cell wall of Gram‐negative bacteria, is closely related to AEC apoptosis .…”

Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation In Vivo

“…Several studies reviewed the protective reagents and methods for EPCs including tripterine, urinary trypsin inhibitor, microRNA-130a, interruption of CD40 pathway, and GM-CSF [68][69][70][71]. As a cholesterol-lowering medicine originally, probucol significantly inhibits the initiation and development of atherosclerosis via multiple mechanisms including suppressing ROS formation [72][73][74], rescuing endothelial function [75][76][77], inhibiting the activation and adhesion of monocytes [78], attenuating growth and migration of VSMCs [76,79,80], altering proliferation and apoptosis of VSMCs [80][81][82] and macrophages [83], as well as decreasing cytokine secretion in macrophages of [84].…”

Somatostatin Reduces the Acute Lung Injury of Mice via Increasing the Affinity of Glucocorticoid Receptor

“…and stem cell [3,4], no specific treatment exists for these diseases. Recently, several lines of evidence showed that somatostatin (SOM) has protective effects against central nervous system, pancreatic and gastrointestinal tract diseases [5][6][7], but the role of SOM in ALI remains to be clarified.…”