title: L-Carnitine Protects Renal Tubular Cells Against Calcium Oxalate Monohydrate Crystals Adhesion Through Preventing Cells From Dedifferentiation.
abstract: OBJECTIVE
  The interactions between calcium oxalate monohydrate (COM) crystals and renal tubular epithelial cells are important for renal stone formation but still unclear. This study aimed to investigate changes of epithelial cell phenotype after COM attachment and whether L-carnitine could protect cells against subsequent COM crystals adhesion.
  
  
  METHODS
  Cultured MDCK cells were employed and E-cadherin and Vimentin were used as markers to estimate the differentiate state. AlexaFluor-488-tagged COM crystals were used in crystals adhesion experiment to distinguish from the previous COM attachment, and adhesive crystals were counted under fluorescence microscope, which were also dissolved and the calcium concentration was assessed by flame atomic absorption spectrophotometry.
  
  
  RESULTS
  Dedifferentiated MDCK cells induced by transforming growth factor β1 (TGF-β1) shown higher affinity to COM crystals. After exposure to COM for 48 hours, cell dedifferentiation were observed and more subsequent COM crystals could bind onto, mediated by Akt/GSK-3β/Snail signaling. L-carnitine attenuated this signaling, resulted in inhibition of cell dedifferentiation and reduction of subsequent COM crystals adhesion.
  
  
  CONCLUSIONS
  COM attachment promotes subsequent COM crystals adhesion, by inducing cell dedifferentiation via Akt/GSK-3β/Snail signaling. L-carnitine partially abolishes cell dedifferentiation and resists COM crystals adhesion. L-carnitine, may be used as a potential therapeutic strategy against recurrence of urolithiasis.
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University. Guangdong Key Laboratory of Urology.
authors.forename: Shujue
authors.initials: S
authors.lastname: Li
authors.forename: Wenqi
authors.initials: W
authors.lastname: Wu
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Wu
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Duan
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Kong
authors.forename: Guohua
authors.initials: G
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism*; D002331:Carnitine / Q000502:physiology*; D002448:Cell Adhesion; D054337:Cell Dedifferentiation; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D007684:Kidney Tubules / Q000166:cytology*; D061985:Madin Darby Canine Kidney Cells; D020011:Protective Agents / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020011:Protective Agents; D002129:Calcium Oxalate; D051057:Proto-Oncogene Proteins c-akt; D002331:Carnitine