title: 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.
authors.affiliation: Guangdong Geriatrics Institute, Guangdong General Hospital, Guangdong Academy of Medical sciences No. 106, Zhongshan Road, Guangzhou, China.
authors.forename: Weixin
authors.initials: W
authors.lastname: Guo
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xie
authors.forename: Tiehe
authors.initials: T
authors.lastname: Qin
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Chai
authors.forename: Frank
authors.initials: F
authors.lastname: Yi
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Shouhong
authors.initials: S
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects / Q000648:ultrastructure; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D004801:Eosine Yellowish-(YS); D015870:Gene Expression; D006023:Glycoproteins / Q000494:pharmacology*; D006416:Hematoxylin; D006651:Histocytochemistry; D007275:Injections, Intravenous; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D019301:Oleic Acid; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006023:Glycoproteins; D019301:Oleic Acid; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; C028665:urinastatin; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin