Involvement of the Ubiquitin-Proteasome System in the Formation of Experimental Postsurgical Peritoneal Adhesions

Marco Ferretti,Clara Di Filippo,Michele D'Amico,Francesco Rossi,Pasquale Petronella,Sivestro Canonico,Fulvio Freda,Marco Scorzelli

doi:10.1155/2012/194723

Marco Ferretti, Clara Di Filippo + Show 6 more

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https://doi.org/10.1155/2012/194723

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Abstract

We investigated the Ubiquitin-Proteasome System (UPS), major nonlysosomal intracellular protein degradation system, in the genesis of experimental postsurgical peritoneal adhesions. We assayed the levels of UPS within the adhered tissue along with the development of peritoneal adhesions and used the specific UPS inhibitor bortezomib in order to assess the effect of the UPS blockade on the peritoneal adhesions. We found a number of severe postsurgical peritoneal adhesions at day 5 after surgery increasing until day 10. In the adhered tissue an increased values of ubiquitin and the 20S proteasome subunit, NFkB, IL-6, TNF-α and decreased values of IkB-beta were found. In contrast, bortezomib-treated rats showed a decreased number of peritoneal adhesions, decreased values of ubiquitin and the 20S proteasome, NFkB, IL-6, TNF-α, and increased levels of IkB-beta in the adhered peritoneal tissue. The UPS system, therefore, is primarily involved in the formation of post-surgical peritoneal adhesions in rats.

Highlights

Postsurgical adhesions are polymorphic clinical pictures ranging from abdominal and pelvic pain to intestinal mechanical occlusion
We hypothesized that the activation of this system during the surgery can be suggestive of the beginning of inflammatory events that in cascade lead to adhesions formation. In this experimental study on rats we have evaluated whether changes in Ubiquitin-Proteasome System (UPS) levels and activity into the adhered tissue occur along with the development of post-surgical peritoneal adhesions, and we used the specific UPS inhibitor bortezomib [15,16,17] in order to ascertain the role that the UPS may have in the peritoneal adhesions formation
The qualitative evaluation by the peritoneal adhesions score indicates a substantial decrease of adhesions in the group of rats treated with bortezomib (e.g., 4 rats were scored 6 and 2 rats were scored 5) after 10 days of surgery if compared with the control group same day (Figure 2)

Summary

Introduction

Postsurgical adhesions are polymorphic clinical pictures ranging from abdominal and pelvic pain to intestinal mechanical occlusion. They are due to stable lesions scarring, the adhesions. Adhesions formation is initiated by the trauma surgery, and it is supported by a number of factors including fibrin, thromboplastin, mesothelial cells, fibroblasts, collagen fibrils, and the development of a local inflammatory process, among others [3]. Until a few years ago to prevent the formation of adhesions, the focus was mainly on the procedures to be implemented during surgery. It is worth mentioning that there is considerable consensus that laparoscopic surgery is associated with the reduced development of adhesions compared to open surgery in the international arena [4, 5]

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