Mascetta G, di Mola F F, Tavano F, Selvaggi F, Giese N, Bassi C, Büchler M W, Friess H, di Sebastiano P
Department of Surgery, IRCCS, Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Eur Surg Res. 2012;48(3):131-8. doi: 10.1159/000337869. Epub 2012 May 8.
BACKGROUND/AIMS: We aimed to analyze substance P (SP) and neprilysin (NEP), the membrane metallopeptidase that degrades SP, in chronic pancreatitis (CP).
SP and NEP mRNA levels were analyzed by qRT-PCR in tissue samples from 30 patients with CP and 8 organ donors. In addition, SP serum levels were determined before and after surgery in the same patients, by means of a competitive ELISA assay. Genetic and epigenetic analyses of the NEP gene were also performed.
SP mRNA expression levels were higher in CP tissues compared to controls (p = 0.0152), while NEP mRNA showed no significant differences between CP and healthy subjects (p = 0.2102). In CP patients, SP serum levels correlated with those in tissue, and after surgical resection SP serum levels were reduced compared to the preoperative values. Failure of NEP to overexpress in CP tissues was associated with significant miR-128a overexpression (p = 0.02), rather than with mutations in the NEP coding region or the presence of hypermethylation sites in the NEP promoter region.
Tissue and serum levels of SP were increased in CP, while NEP levels remained unaltered. In an SP/NEP-mediated pathway, it would appear that NEP fails to provide adequate surveillance of SP levels. Failure of NEP to overexpress could be associated with miRNA regulation.
背景/目的：我们旨在分析慢性胰腺炎（CP）中P物质（SP）和中性内肽酶（NEP，一种可降解SP的膜金属肽酶）。
采用qRT-PCR分析了30例CP患者和8例器官捐献者组织样本中SP和NEP的mRNA水平。此外，通过竞争性ELISA检测法测定了同一批患者手术前后的血清SP水平。还对NEP基因进行了遗传和表观遗传分析。
与对照组相比，CP组织中SP mRNA表达水平更高（p = 0.0152），而CP患者与健康受试者之间NEP mRNA无显著差异（p = 0.2102）。在CP患者中，血清SP水平与组织中的水平相关，手术切除后血清SP水平较术前降低。CP组织中NEP未能过表达与miR-128a显著过表达相关（p = 0.02），而非与NEP编码区突变或NEP启动子区域存在高甲基化位点有关。
CP患者组织和血清中SP水平升高，而NEP水平保持不变。在SP/NEP介导的途径中，似乎NEP未能对SP水平进行充分监测。NEP未能过表达可能与miRNA调控有关。
