title: Up-regulated mTOR pathway indicates active disease in both human native and transplant kidneys.
abstract: BACKGROUND
  Recent studies show that up-regulated mammalian target of rapamycin (mTOR) indicates cellular repair and senescence, possibly through interaction with reactive oxygen species and autophagy in vivo and in vitro. In human native and transplant biopsies, we investigated whether injured renal tissue had activated mTOR complex 1 (mTORC1) branch of mTOR pathway in glomerular and tubular epithelia.
  
  
  METHODS
  A total of 238 native and transplant renal sections were stained for phosphorylated (p)-mTOR and two downstream signals, p-p70S6K and p-4EBP, of the mTORC1 branch. The signals' expressions were correlated with several clinical factors.
  
  
  RESULTS
  There was significant up-regulation of all three makers in the tubular epithelium and in glomerular visceral and parietal epithelium in both native and transplant biopsies when compared to controls. The up-regulated mTOR activity was significantly correlated with serum creatinine levels and interstitial fibrosis but not with proteinuria levels.
  
  
  CONCLUSIONS
  The up-regulated mTOR activity (limited to mTORC1 branch) in all glomerular and tubular epithelia from both transplant and native biopsies indicates that the activated mTOR signaling is a general phenomenon in variants of progressing renal diseases and may be used as a marker of active renal disease states.
authors.affiliation: PhD; Department of Anatomic Pathology, William Beaumont Hospital, 3601 W. 13 Mile Rd., Royal Oak, MI, USA; phone: 248-898-9060; fax: 248-898-8020; e mail: ping.zhang@beaumont.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Ping L
authors.initials: PL
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000175:diagnosis* / Q000378:metabolism; D009399:Nephrons / Q000378:metabolism*; D012189:Retrospective Studies; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013781:Texas; D019737:Transplants / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: mTOR activity; native biopsy; proteinuria; renal failure; transplant biopsy