MMPs/TIMPs and inflammatory signalling de-regulation in human incisional hernia tissues
Guillen-Marti, Jordi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Diaz, Ramon (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Quiles, Maria T.. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
López Cano, Manuel (Hospital Universitari Vall d'Hebron)
Vilallonga, Ramon (Hospital Universitari Vall d'Hebron)
Huguet, Pere (Hospital Universitari Vall d'Hebron)
Ramon-y-Cajal, Santiago (Hospital Universitari Vall d'Hebron)
Sanchez-Niubo, Albert (Institut Hospital del Mar d'Investigacions Mèdiques)
Reventós, Jaume (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Armengol Carrasco, Manuel (Hospital Universitari Vall d'Hebron)
Arbós i Via, Maria Antònia (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Data:	2008
Resum:	Background: Incisional hernia is a common and important complication of laparotomies. Epidemiological studies allude to an underlying biological cause, at least in a subset of population. Interest has mainly focused on abnormal collagen metabolism. However, the role played by other determinants of extracellular matrix (ECM) composition is unknown. To date, there are few laboratory studies investigating the importance of biological factors contributing to incisional hernia development. We performed a descriptive tissue-based analysis to elucidate the possible relevance of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in association with local cytokine induction in human incisional hernia tissues. The expression profiles of MMPs, TIMPs and pro-inflammatory cytokine signalling were investigated in aponeurosis and skeletal muscle specimens taken intraoperatively from incisional hernia (n = 10) and control (n = 10) patients. Semiquantitative RT-PCR, zymography and immunoblotting analyses were done. Incisional hernia samples displayed alterations in the microstructure and loss of ECM, as assessed by histological analyses. Moreover, incisional hernia tissues showed increased MMP/TIMP ratios and de-regulated inflammatory signalling (tumor necrosis factor [TNFA] and interleukin [IL]-6 tended to increase, whereas aponeurosis TNFA receptors decreased). The changes were tissue-specific and were detectable at the mRNA and/or protein level. Statistical analyses showed several associations between individual MMPs, TIMPs, interstitial collagens and inflammatory markers. The increment of MMPs in the absence of a counterbalance by TIMPs, together with an ongoing de-regulated inflammatory signalling, may contribute in inducing a functional defect of the ECM network by post-translational mechanisms, which may trigger abdominal wall tissue loss and eventual rupture. The notable TIMP3 protein down-regulation in incisional hernia fascia may be of pathophysiological significance. We conclude that this study may help to pinpoint novel hypotheses of pathogenesis that can lead to a better understanding of the disease and ultimately to improvement in current therapeutic approaches.
Ajuts:	Instituto de Salud Carlos III PI030290 Instituto de Salud Carlos III PI070507
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Incisional hernia ; Extracellular matrix ; Aponeurosis ; Skeletal muscle ; MMP/TIMP ; TNFA ; TNFRSFs ; IL-6
Publicat a:	Journal of Cellular and Molecular Medicine, Vol. 13 (12 2008) , p. 4432-4443, ISSN 1582-4934

DOI: 10.1111/j.1582-4934.2008.00637.x
PMID: 19397782

12 p, 786.4 KB

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