title: Intracellular kinases mediate increased translation and secretion of netrin-1 from renal tubular epithelial cells.
abstract: BACKGROUND
  Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and mouse kidney cell line (TKPTS) to determine the signaling pathways that regulate netrin-1 production in response to injury.
  
  
  RESULTS
  Ischemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1 production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug induced netrin-1 mRNA translation increase without altering mRNA stability.
  
  
  CONCLUSIONS
  Our results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells.
authors: Vascular Biology Center, Georgia Health Sciences University, Augusta, Georgia, United States of America.
authors: Calpurnia
authors: C
authors: Jayakumar
authors: Riyaz
authors: R
authors: Mohamed
authors: Punithavathi Vilapakkam
authors: PV
authors: Ranganathan
authors: Ganesan
authors: G
authors: Ramesh
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism*; D007668:Kidney / Q000293:injuries* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000075388:Netrin-1; D020871:RNA Stability; D015427:Reperfusion Injury; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D020928:Mitogen-Activated Protein Kinases