The gene expression profile of matrix metalloproteinases and their inhibitors in children with Henoch-Schönlein purpura

Br J Dermatol. 2011 Jun;164(6):1348-55. doi: 10.1111/j.1365-2133.2011.10295.x.

Abstract

Background: Because inflammatory cytokines are known to be potent inducers of matrix metalloproteinases (MMPs), and MMPs themselves can promote inflammation, we speculated that MMP activation might be involved in the pathogenesis of Henoch-Schönlein purpura (HSP) vasculitis.

Objectives: To investigate the gene expression profile of all known MMPs and tissue inhibitors of metalloproteinases (TIMPs) in children with HSP and to examine the role, if any, of MMPs in the pathogenesis of HSP.

Methods: Peripheral blood samples were obtained from 10 patients with HSP (nine were in the acute stage, one had HSP nephritis) and four healthy controls. Peripheral blood samples were also taken from the nine patients with HSP when they reached the convalescent stage of the disease. From these samples, total RNA was purified and gene expressions were measured using real-time polymerase chain reaction.

Results: MMP-8 expression was decreased in patients with arthralgia (P = 0·038), and MMP-3 (P = 0·03) and TIMP-4 expressions (P = 0·016) were elevated in HSP patients with nephritis. Soft tissue oedema was associated with decreased expressions of MMP-26 (P = 0·038) and MMP-28 (P = 0·038). MMP-1, MMP-8, MMP-9, MMP-10, MMP-13, MMP-16 and MMP-26 levels were significantly higher in patients in the acute stage of HSP than in normal controls (P < 0·05). MMP-9 (P = 0·097) and MMP-19 (P = 0·054) levels decreased to borderline significance in patients in the convalescent stage compared with those in the acute stage. The duration of steroid administration was negatively correlated with MMP-1, MMP-2, MMP-7, MMP-10, MMP-12, MMP-19, MMP-23 and TIMP-1 levels (P < 0·05), suggesting a suppressive effect of steroids on the expressions of MMPs and TIMPs.

Conclusions: This is the first study to describe the expression profile of all known MMPs and TIMPs in children with HSP, and our results suggested that abnormal levels of MMP and TIMP activity may have a role in the pathogenesis of HSP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Pain / genetics
  • Acute Disease
  • Arthralgia / genetics
  • Case-Control Studies
  • Child
  • Child, Preschool
  • DNA, Complementary / metabolism
  • Edema / genetics
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Male
  • Matrix Metalloproteinases / genetics*
  • Matrix Metalloproteinases / metabolism
  • Nephritis / genetics
  • Purpura, Schoenlein-Henoch / genetics*
  • Real-Time Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinases / genetics*
  • Tissue Inhibitor of Metalloproteinases / metabolism

Substances

  • DNA, Complementary
  • Tissue Inhibitor of Metalloproteinases
  • Matrix Metalloproteinases