Matrix Metalloproteinase 9 and Vasodilator-Stimulated Phosphoprotein Related to Acute Kidney Injury in Severe Acute Pancreatitis Rats

Dig Dis Sci. 2015 Dec;60(12):3647-55. doi: 10.1007/s10620-015-3820-8. Epub 2015 Aug 12.

Abstract

Background: Severe acute pancreatitis (SAP) usually results in acute renal failure. Matrix metalloproteinase 9 (MMP-9) and vasodilator-stimulated phosphoprotein (VASP) may participate in disease progression.

Aim: To investigate the renal expression of MMP-9 and VASP in SAP rats with acute kidney injury.

Methods: A total of 100 rats were randomly assigned to sham 6-h, sham 12-h, sham 24-h, sham 36-h, sham 48-h, SAP 6-h, SAP 12-h, SAP 24-h, SAP 36-h, and SAP 48-h treatment groups (n = 10 per group). Levels of serum amylase (AMY), creatinine (Cr), and blood urea nitrogen (BUN) were determined. Renal pathology and ultrastructural examinations were performed, and renal mRNA and protein expression of MMP-9 and VASP were determined by real-time RT-PCR and Western blot, respectively. The activity of MMP-9 was assessed by gelatin zymography.

Results: In the SAP groups, serum levels of AMY, Cr, and BUN were markedly higher than in the sham groups. The peak value of AMY was observed from 12 to 24 h, but that of Cr and BUN was observed at 36 h. Capillary endothelial cells in the renal interstitium were impaired and expression of MMP-9 and VASP in the kidney was significantly increased when compared with the sham groups. Expression of MMP-9 and VASP declined when renal damage reached a maximum after 24 h.

Conclusions: In the presence of acute kidney injury in SAP, the renal expression of MMP-9 and VASP is related to damage of endothelial cells in capillaries, which reached a maximum at 24 h and declined afterwards.

Keywords: Acute kidney injury; Endothelial cells; MMP-9; Severe acute pancreatitis; VASP.

MeSH terms

  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Gene Expression Regulation
  • Kidney / pathology
  • Kidney / ultrastructure
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Pancreatitis / complications*
  • Pancreatitis / metabolism
  • Pancreatitis / pathology
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cell Adhesion Molecules
  • Microfilament Proteins
  • Phosphoproteins
  • RNA, Messenger
  • vasodilator-stimulated phosphoprotein
  • Matrix Metalloproteinase 9