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Kidney Week

Abstract: TH-PO009

Knockout of Leucine Rich α-2 Glycoprotein Protects Against Renal Ischemia-Reperfusion Injury Through Reduction of Fibrosis and Apoptosis

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Takeshi, Kahio, Kochi Medical School Hospital, Nankoku-shi, Japan
  • Terada, Yoshio, Kochi Medical School, Nankoku-city, Japan
  • Fujimoto, Shimpei, Kochi University, Nankoku, Japan
  • Taniguchi, Yoshinori, Kochi University, Nankoku, Japan
  • Ogasawara, Masami, Kochi University, Nankoku, Japan
  • Horino, Taro, Kochi Medical School, Kochi University, Kochi, Japan
  • Nishikawa, Hirofumi, Kochi University, Nankoku, Japan
  • Shimamura, Yoshiko, Kochi Medical School, Kochi University, Kochi, Japan
  • Matsumoto, Tatsuki, Kochi University, Nankoku, Japan

Leucine-rich α-2 glycoprotein (LRG) is one of serum glycosylated proteins with 347 amino acids, and serum LRG is reported as a novel disease activity biomarker for inflammatory bowel disease. However, little is known about the role of LRG in acute kidney injury (AKI) pathogenesis. We examined renal LRG expression and urinary LRG level using mice AKI model and clinical samples.


We evaluated LRG function in the bilateral renal ischemia-reperfusion injury (IRI) AKI model by using LRG knockout (KO) and wild-type (WT) mice. We at first evaluate the localization of LRG in AKI of WT mice. The effects of LRG on phosphorylation of Smads were examined in primary cultured renal tubular cells. In clinical study, we measured urine LRG in AKI patients, and immunohistological examination of LRG in AKI and minimal change renal biopsy sample.


In WT mice with IRI-induced AKI, renal mRNA and protein expression of LRG were induced from 6 h and 12 h and peaked at 24 h and 48 h after IRI, respectively. In control mice kidney, only a very few expression of LRG was observed. Urine and serum LRG are increased after IRI in WT mice. Immunohistological examination showed that LRG expression was observed mainly in renal distal tubular cells in AKI mice. LRG KO mice had significantly lower PCr (0.61+0.13 versus 1.67+0.38 mg/dl), BUN (102.3+21.8 versus 234.5+48.5 mg/dl) at 48h after IRI compared to WT mice. Immunohistological examination showed mild tubular injury, fibrotic change, collagen IV deposition, and fewer KIM-1 positive and apoptotic cells in LRG KO mice. In primary cultured renal tubular cells, TNF-a and LPS stimulated LRG expression. LRG KO reduced TGF-b stimulated-phosphorylation of Smad2. Notably, in contrast media-induced AKI patients, urinary LRG levels were increased from 6 h. LRG staining were enhanced in AKI renal-biopsy samples.


Our results demonstrate that LRG is up-regulated in renal tissues in both mice and human AKI, and that urine and serum LRG are increased in early phase of AKI. Inflammatory cytokines such as TNF- a stimulates expression of LRG in renal tubular cells. Thus, LRG could serve as a potential early biomarker in AKI, and LRG blockage could serve as a potential therapeutic target in AKI.