title: Hypoxia inducible factor-1 alpha promotes mesangial cell proliferation in lupus nephritis.
abstract: BACKGROUND
  Evidence has accumulated that hypoxia plays a significant role in the pathogenesis and progression of both acute renal injury and chronic renal disease. However, little was known about the effects of hypoxia on lupus nephritis (LN). In the current study, we investigated the expression of hypoxia inducible factor-1 alpha (HIF-1α) in LN.
  
  
  METHODS
  Renal biopsies from 22 LN patients and 20 patients with renal carcinoma were obtained. In situ HIF-1α expression was examined by immunohistochemical staining, and the relationship between HIF-1α and clinical/pathological features was analyzed. HIF-1α expression in kidney from both MRL/lpr and C57BL/6 mice was detected by immunohistochemical technology. Dimethyloxaloylglycine (DMOG), an inhibitor of HIF-degrading prolylhydroxylases, was utilized to prevent HIF-1α degradation in mouse mesangial cells (MCs). After DMOG treatment, the proliferation and apoptosis rates of mouse MCs were determined.
  
  
  RESULTS
  LN patients showed larger amounts of HIF-1α in both glomerular and tubulointerstitial areas. The levels of intraglomerular HIF-1α were closely associated with renal pathology activity index and clinical manifestations in LN patients. In MRL/lpr mice, intraglomerular HIF-1α-positive cells were also significantly increased. Interestingly, the levels of HIF-1α positively correlated with cell density in glomerulus in both LN patients and MRL/lpr mice. Upon treatment with DMOG, the proliferation of MCs was upregulated, and apoptosis was downregulated.
  
  
  CONCLUSIONS
  HIF-1α is highly expressed in both glomerular and tubulointerstitial tissues in LN, especially in proliferative LN. HIF-1α may promote MCs growth through the induction of proliferation and inhibition of apoptosis, and hence plays an important role in the pathogenesis of LN.
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Yile
authors.initials: Y
authors.lastname: Ren
authors.forename: Xuebing
authors.initials: X
authors.lastname: Feng
authors.forename: Genhong
authors.initials: G
authors.lastname: Yao
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Hengjin
authors.initials: H
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
mesh_terms: D000328:Adult; D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000737:chemistry*; D007684:Kidney Tubules / Q000737:chemistry; D008181:Lupus Nephritis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D050527:Mesangial Cells / Q000737:chemistry; D051379:Mice; D064800:Prolyl-Hydroxylase Inhibitors / Q000494:pharmacology; D011507:Proteinuria / Q000209:etiology; D012709:Serum Albumin / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D000600:Amino Acids, Dicarboxylic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064800:Prolyl-Hydroxylase Inhibitors; D012709:Serum Albumin; C040947:oxalylglycine