PERINFIB: FISIOPATOLOGIA MOLECULAR DE LA INFLAMACION Y FIBROSIS PERITONEAL

Centro de Biología Molecular Severo Ochoa. Consejo Superior de Investigaciones Cientificas
Investigador Principal: Manuel Lopez Cabrera


Lineas de investigación

Página web del grupo     http://www2.cbm.uam.es/mkfactory.esdomain/webs/CBMSO/plt_LineasInvestigacion.as    px?IdObjeto=113


Objetivo

  • Profundizar en el conocimiento de las implicaciones patológicas de la transición Epitelio Mesenquima (TEM) de las células mesoteliales y de los mecanismos     moleculares que regulan dicho proceso y la identificación de dianas moleculares para el diseño de estrategías terapéuticas, con posibles aplicaciones en     enfermedades que cursan con la fibrosis/angiogénesis peritoneal y en la metástasis peritoneal.

 

Componentes

  • Manuel López Cabrera
  • Maria Luisa Pérez
  • Pilar Sandoval
  • Abelardo Isaac Aguilera Peralta
  • Angela Rynne Vidal
  • Georgios Liappas

 

Publicaciones más relevantes 2013-2015

  1. Fierro-Fernández M, Busnadiego Ó, Sandoval P, Espinosa-Díez C, Blanco-Ruiz E, Rodríguez M, Pian H, Ramos R, López-Cabrera M, García-Bermejo ML, Lamas S. miR-9-5p suppresses pro-fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2. EMBO Rep. 2015;16(10):1358-77.
  2. González-Santamaría J, Villalba M, Busnadiego O, López-Olañeta MM, Sandoval P, Snabel J, López-Cabrera M, Erler JT, Hanemaaijer R, Lara-Pezzi E, Rodríguez-Pascual F. Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction. Cardiovasc Res. 2015. pii: cvv214.
  3. Liappas G, Gónzalez-Mateo GT, Majano P, Sánchez-Tomero JA, Ruiz-Ortega M, Rodrigues Díez R, Martín P, Sanchez-Díaz R, Selgas R, López-Cabrera M, Aguilera Peralta A. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage. Biomed Res Int. 2015; :416480.
  4. Busnadiego O, Gorbenko Del Blanco D, González-Santamaría J, Habashi JP,Calderon JF, Sandoval P, Bedja D, Guinea-Viniegra J, Lopez-Cabrera M, Rosell-Garcia T, Snabel JM, Hanemaaijer R, Forteza A, Dietz HC, Egea G, Rodriguez-Pascual F. Elevated expression levels of lysyl oxidases protect against aortic aneurysm progression in Marfan syndrome. J Mol Cell Cardiol. 2015 :48-57.
  5. Strippoli R, Loureiro J, Moreno V, Benedicto I, Pérez Lozano ML, Barreiro O, Pellinen T, Minguet S, Foronda M, Osteso MT, Calvo E, Vázquez J, López Cabrera M, del Pozo MA. Caveolin-1 deficiency induces a MEK-ERK1/2-Snail-1-dependent epithelial-mesenchymal transition and fibrosis during peritoneal dialysis. EMBO Mol Med. 2014 Dec 30;7(1):102-23. doi: 10.15252/emmm.201404127. Erratum in: EMBO Mol Med. 2015; 7(3):357
  6. González-Mateo GT, Fernández-Míllara V, Bellón T, Liappas G, Ruiz-Ortega M, López-Cabrera M, Selgas R, Aroeira LS. Paricalcitol reduces peritoneal fibrosis in mice through the activation of regulatory T cells and reduction in IL-17 production. PLoS One. 2014 Oct 3;9(10):e108477. doi: 10.1371/journal.pone.0108477. eCollection 2014.
  7. Busnadiego O, Loureiro-Álvarez J, Sandoval P, Lagares D, Dotor J, Pérez-Lozano ML, López-Armada MJ, Lamas S, López-Cabrera M, Rodríguez-Pascual F. A pathogenetic role for endothelin-1 in peritoneal dialysis-associated fibrosis. J Am Soc Nephrol. 2015; 26(1):173-82.
  8. Rodrigues-Díez R, Aroeira LS, Orejudo M, Bajo MA, Heffernan JJ, Rodrigues-Díez RR, Rayego-Mateos S, Ortiz A, Gonzalez-Mateo G, López-Cabrera M, Selgas R, Egido J, Ruiz-Ortega M. IL-17A is a novel player in dialysis-induced peritoneal damage. Kidney Int. 2014; 86(2):303-15.
  9. Sandoval P, Jiménez-Heffernan JA, Rynne-Vidal Á, Pérez-Lozano ML, Gilsanz Á, Ruiz-Carpio V, Reyes R, García-Bordas J, Stamatakis K, Dotor J, Majano PL, Fresno, M, Cabañas C, López-Cabrera M. Carcinoma-associated fibroblasts derive from mesothelial cells via mesothelial-to-mesenchymal transition in peritoneal metastasis. J Pathol. 2013; 231(4):517-31.
  10. Loureiro J, Sandoval P, del Peso G, Gónzalez-Mateo G, Fernández-Millara V, Santamaria B, Bajo MA, Sánchez-Tomero JA, Guerra-Azcona G, Selgas R, López-Cabrera M, Aguilera AI. Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis. PLoS One. 2013 Apr 23;8(4):e61165.
  11. Pérez-Lozano ML, Sandoval P, Rynne-Vidal A, Aguilera A, Jiménez-Heffernan JA, Albar-Vizcaíno P, Majano PL, Sánchez-Tomero JA, Selgas R, López-Cabrera M. Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition. PLoS One. 2013; 8(4):e60776.

Publicaciones más relevantes 2010-2012

  1. Molina-Jiménez F, Benedicto I, Thi VLD, Gondar V, Lavillette D, Marín JJG, Briz O, Moreno-Otero R, Aldabe R, Baumert TF, Cosset FL, López-Cabrera M and Majano PL. Matrigel-embedded 3D culture of hepatoma-derived cell lines as a hepatocyte-like polarized system to study hepatitis C virus cycle. Virology,  2012, 425 (1): 31-9.
  2. Strippoli R, Benedicto I, Perez-Lozano ML, Pellinen T, Lopez-Cabrera M and del Pozo MA. Inhibition of transforming growth factor-activated kinase 1 (TAK1) blocks and reverses epithelial to mesenchymal transition of mesothelial cells. PLoS One, 2012; 7 (2) e31492
  3. Fernandez-Perpen A, Perez-Lozano ML, Bajo MA, Albar-Vizcaino P, Sandoval P, del Peso G, Castro MJ, Aguilera A, Ossorio M, Peter ME, Passlick-Deetjen J, Aroeira LS, Selgas R, Lopez-Cabrera M, Sanchez-Tomero JA. Influence of bicarbonate-low-GDPs peritoneal dialysis fluid (Bicavera®) on in vitro and ex vivo epithelial-to-mesenchymal transition of mesothelial cells Perit Dial Int  2012
  4. Loureiro J, Aguilera A, Selgas R, Sandoval P, Albar-Vizcaíno P, Pérez-Lozano ML, Ruíz-Carpio V, Majano PL, Lamas S, Rodríguez-Pascual F, Borras-Cuesta F, Dotor J, López-Cabrera M. Blocking TGF-β1 Protects the Peritoneal Membrane from Dialysate-Induced Damage. J Am Soc Nephrol. 22: 682-695. 2011.
  5. Bajo MA, Pérez-Lozano ML, Albar-Vizcaino P, Del Peso G, Castro MJ, Gonzalez-Mateo G, Fernández-Perpén A, Aguilera A, Sánchez-Villanueva R, Sánchez-Tomero JA, López-Cabrera M, Peter ME, Passlick-Deetjen J, Selgas R. Low-GDP peritoneal dialysis fluid ('balance') has less impact in vitro and ex vivo on epithelial-to-mesenchymal transition (EMT) of mesothelial cells than a standard fluid. Nephrol Dial Transplant. 26: 282-291. 2011.
  6. Aguilera A, González–Espinoza L, Codoceo R, Jara MC, Pavone M, Bajo MA, Del Peso G, Celadilla O, Martínez MV, López–Cabrera M, Selgas R. Bowel bacterial overgrowth as another cause of malnutrition, inflammation, and atherosclerosis syndrome in peritoneal dialysis patients. Adv. Perit Dial 26: 130-136. 2010.
  7. Strippoli R, Benedicto I, Foronda M, Pérez-Lozano ML, Sánchez-Perales S, López-Cabrera M, del Pozo MA. p38 maintains E-cadherin expression by modulating TAK1–NF-kB during epithelial-to-mesenchymal transition. J Cell Science 123: 4321-4331. 2010.
  8. Sandoval P, Loureiro J, González-Mateo G, Pérez-Lozano ML, Maldonado-Rodríguez A, Sánchez-Tomero JA, Mendoza L, Santamaría B, Ortiz A, Ruíz-Ortega M, Selgas R, Martín P, Sánchez-Madrid F, Aguilera A, López-Cabrera M. PPAR-gamma agonist rosiglitazone protects peritoneal membrane from dialysis fluid-induced damage. Lab Invest 90: 1517-1532. 2010.
  9. Molina-Jiménez F, Benedicto I, Murata M, Martín-Vílchez S, Seki T, Pintor-Toro JA, Tortolero M, Moreno-Otero R, Okazaki K, Koike K, Barbero JL, Matsuzaki K. Majano PL, López-Cabrera M. Expression of pituitary tumor-transforming gene 1 (PTTG1)/securin in hepatitis B virus (HBV)-associated liver diseases: evidence for an HBV X protein-mediated inhibition of PTTG1 ubiquitination and degradation. Hepatology 51: 777-787. 2010.
  10. Loureiro J, Schilte M, Aguilera A, Albar-Vizcaíno P, Ramírez-Huesca M, Pérez-Lozano ML, González-Mateo G, Aroeira LS, Selgas R, Mendoza L, Ortiz A, Ruíz-Ortega M, van den Born J, Beelen RHJ and López-Cabrera M. BMP-7 blocks mesenchymal conversion of mesothelial cells and prevents peritoneal damage induced by dialysis fluid exposure. Nephrol Dial Transplant 25: 1098-1108. 2010