Expression of profibrotic genes in a murine remnant kidney model

Binxia Yang, Pawan K. Vohra, Rajiv Janardhanan, Khamal D. Misra, Sanjay Misra

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Purpose: To test the hypothesis that there is increased expression of several profibrotic genes, including matrix metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2), a disintegrin and metalloproteinase with thrombospondin motif-1 (ADAMTS-1), and fibroblast specific protein-1 (FSP-1) in a murine remnant kidney model. Materials and Methods: Chronic kidney disease (CKD) was created in 10 C57BL/6 male mice (2025 g) by performing a right nephrectomy and ligation of the upper pole of the left kidney (remnant kidney). Animals were sacrificed 42 days and 56 days later. Reverse transcriptase polymerase chain reaction (RT-PCR) for MMP-2, MMP-9, TIMP-1, TIMP-2, ADAMTS-1, and FSP-1 was performed in the remnant kidney. Histologic evaluation of the remnant kidney was performed using Ki-67, α-smooth muscle cell actin (α-SMA), hematoxylin and eosin, and Masson' trichrome staining. Kidney function was assessed using serum blood urea nitrogen (BUN) and creatinine. Results: The mean serum BUN and creatinine levels at day 42 and day 56 were significantly higher than baseline (P <.05). By day 42, the mean expression of MMP-2, MMP-9, TIMP-1, ADAMTS-1, and FSP-1 was significantly higher in the remnant kidney compared with the normal kidney (P <.05); by day 56, only FSP-1 expression was significantly higher (P <.05). There was increased fibrosis by Masson' trichrome, increased Ki-67, and increased α-SMA staining in the remnant kidney compared with the normal kidney. Conclusions: In the remnant kidney, there was increased fibrosis with increased α-SMA and Ki-67 staining and significantly increased expression of MMP-2, MMP-9, TIMP-1, ADAMTS-1, and FSP-1.

Original languageEnglish (US)
Pages (from-to)1765-1772.e1
JournalJournal of Vascular and Interventional Radiology
Volume22
Issue number12
DOIs
StatePublished - Dec 2011

Keywords

  • ADAMTS-1
  • BUN
  • CKD
  • FSP-1
  • MMP
  • PCR
  • RNA
  • RT-PCR
  • SEM
  • TIMP
  • VEGF-A
  • a disintegrin and metalloproteinase with thrombospondin motif-1
  • blood urea nitrogen
  • cDNA
  • chronic kidney disease
  • complementary deoxynucleic acid
  • fibroblast specific protein-1
  • mRNA
  • matrix metalloproteinase
  • messenger ribonucleic acid
  • polymerase chain reaction
  • reverse transcriptase polymerase chain reaction
  • ribonucleic acid
  • standard error of mean
  • tissue inhibitor of metalloproteinase
  • vascular endothelial growth factor-A
  • α-SMA
  • α-smooth muscle actin

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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