Alterations in fibrinolytic system proteins PAI-1, MMP-3, MMP-8, TIMP-1 and TIMP-2 in post-cholecystectomy bile duct injury
José Manuel Hermosillo-Sandoval, Luis Miguel Román-Pintos, Adolfo Daniel Rodríguez-Carrizález, Ernesto Germán Cardona-Muñoz, Fermín Paul Pacheco-Moisés, Genaro Gabriel Ortiz, Alejandra Guillermina Miranda-Díaz
Department of Surgery, Specialties Hospital of the National Occidental Medical Centre, Social Security Institute of Mexico (Departamento de Cirugía, Hospital de Especialidades del Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social), Guadalajara, México.
Pathology and Oxidative Stress Laboratory, Division of Neurosciences, Occidental Biomedical Research Centre, Social Security Institute of Mexico (Laboratorio de Estrés Oxidativo & Patología, División de Neurociencias, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social), Guadalajara, México.
University Centre for Exact and Engineering Sciences, University of Guadalajara (Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara), Guadalajara, México.
University Health Sciences Centre, University of Guadalajara (Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara), Guadalajara, México.
DOI: 10.4236/jbise.2013.68A2008   PDF   HTML     3,444 Downloads   4,936 Views  


Introduction: In bile duct injuries (BDI), cholestasis and cholangitis can alter the fibrinolytic system by promoting an increase of extracellular matrix depositions which favor an imbalance between metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Materials and Methods: Levels of PAI-1, MMP-3, MMP-8, TIMP-1 and TIMP-2 in 35 patients with post-cholecystectomy BDI by complete biliary obstruction were measured and compared to a healthy control group. Sirius red staining and immune staining for MMP-3 and MMP-8 were also undertaken in liver biopsies. Results: Levels of PAI-1, TIMP-1, TIMP-2 and MMP-8 were higher in BDI than healthy controls: 15 ± 2 ng/mL vs 7.1 ± 2 ng/mL (p < 0.024); 539 ± 64 ng/mL vs 256 ± 13 ng/mL (p < 0.003); 178.4 ± 79.8 ng/mL vs 98.6 ± 2 ng/mL; and 90 ± 10 ng/mL vs 6.8 ± 2 ng/mL (p < 0.002), respectively. However, serum levels of MMP-3 expression in BDI were decreased 9.0 ± 1 vs. healthy controls 20.3 ± 6 ng/mL (p < 0.001). Morphometric analysis showed that Sirius red staining in BDI was increased 121548.6 ± 20545.4 μm2 vs. 22865.7 ± 3865 μm2 in healthy controls (p < 0.0001), MMP-8 deposition in liver was higher in BDI compared to controls: 233015.2 ± 32953.3 μm2 vs. 30744.2 ± 5810.2 μm2 (p < 0.0001). MMP-3 liver staining in BDI compared to healthy controls was not significant 130837.9 ± 17,484 μm2 vs. 116337.9 ± 24803.3 μm2 (p < 0.55). These results suggest an imbalance between fibrogenic/fibrinolytic protein levels. Interestingly, expression of the fibrinolytic protein MMP-8 was increased in serum and liver biopsies in BDI. Conclusion: We found an imbalance of profibrogenic molecules which promote extracellular matrix deposition. The over-expression of fibrinolytic proteins such as MMP-8 could limit liver fibrosis, preventing hepatic dysfunction in post-cholecystectomy BDI.


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Hermosillo-Sandoval, J. , Román-Pintos, L. , Rodríguez-Carrizález, A. , Cardona-Muñoz, E. , Pacheco-Moisés, F. , Ortiz, G. and Miranda-Díaz, A. (2013) Alterations in fibrinolytic system proteins PAI-1, MMP-3, MMP-8, TIMP-1 and TIMP-2 in post-cholecystectomy bile duct injury. Journal of Biomedical Science and Engineering, 6, 58-67. doi: 10.4236/jbise.2013.68A2008.

Conflicts of Interest

The authors declare no conflicts of interest.


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