Saturday, 16th December 2017
Cell Biology and Immunology

    Molecular pathophysiology of fibrosis


Grupo-400

 


Santiago Lamas

ASciStaff

APublications

 

Research summary:

Our laboratory is interested in the molecular mechanisms leading to fibrogenesis in human pathology. Fibrosis is the final common pathway for many organ diseases including diabetic kidney disease, liver cirrhosis, scleroderma, myocardial sclerosis and idiopathic or inflammatory-mediated pulmonary fibrosis. Evolving from a long-standing interest in the vascular wall and redox biology we have now focused our efforts on understanding how the process of fibrogenesis takes place with an emphasis on the role of microRNAs and their regulation by redox signals in processes such as epithelial to mesenchymal transition, TGF-b signaling and fibroblast to myofibroblast transformation. We employ cellular and animal models for lung, skin and kidney fibrosis. We plan to decipher not only the profile of microRNAs involved in fibrogenesis but also the link between the underlying metabolic cellular changes occurring in the fibrotic process and the triggering of specific redox responses leading to the expression of microRNAs relevant for fibrogenesis.

 

fig01





Animal model in lung fibrosis. Intratracheal administration of the antibiotic bleomycin to mice promotes the development of a progressive lung fibrosis phenotype characterized by the loss of the typical alveolar architecture of the lung and extensive accumulation of extracellular matrix components as assessed by histological examination with hematoxilin and eosin (H&E) and Masson´s trichome histological staining, respectively.

 

 


Recent publications:

  • Fierro-Fernández M, Busnadiego  O, Sandoval P, Espinosa-Diez C, Blanco-Ruiz E, Rodriguez M, Pian H, Ramos R, López-Cabrera M, García-Bermejo ML, Lamas S. miR-9-5p suppresses pro-fibrogenic transformation of fibroblast  and prevents organ fibrosis by targeting NOX4 and  TGFBR2. Embo Reports 2015 16 (10):1358-77.
  • Sánchez-Gómez  FJ, Calvo  E, Bretón-Romero R, Fierro-Fernández M, Anilkumar N, Shah AM, Schröder K, Brandes RP, Vázquez J, Lamas S. NOX-4-dependent hydrogen peroxide  promotes shear stress-induced  SHP2 sulfenylation and eNOS activation. Free Radic Biol Med 2015, 89: 419-430
  • Espinosa-Díez C, Fierro-Fernández M, Sánchez-Gómez F, Rodríguez-Pascual F, Alique M, Ruiz Ortega M, Beraza N, Martínez-Chantar ML, Fernández-Hernando C, Lamas  S. Targeting  of Gamma-Glutamyl-Cysteine Ligase by miR-433 Reduces  Glutthione Biosynthesis  and Promotes  TGF-b-Dependent Fibrogenesis . Antioxid Redox Signal 2014
  • Bretón-Romero R, Acín-Perez R, Rodríguez-Pascual F, Martínez-Molledo M, Brandes RP, Rial E, Enríquez JA, Lamas S. Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells. Biochim Biophys Acta. 1843 (11): 2403-13.
  • 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.
  • P Hernasanz Agustin; A Izquierdo Alvarez; F Javier Sánchez Gómez; E Ramos; T Villa Piña; S Lamas; A Bogdanova; A Martínez Ruiz. Acute hypoxia produces a superoxide burst in cells.Free Radical Biology & Medicine.  201471, pp. 146 -156.
  • R Bretón Romero; S Lamas. Hydrogen peroxide signaling in vascular endothelial cells.Redox Biol. 2014 2, pp. 529 - 534.
  • Sánchez-Gómez FJ,; Espinosa-Díez C,; Dubey M,; Dikshit M; Lamas S. S-glutathionylation: relevance in diabetes and potential role as a biomarker. Biol. Chem.
  • Olmos Y,; Sánchez-Gómez FJ,; Wild B; García-Quintans N,; Cabezudo S; Lamas S,; Monsalve M.SirT1 Regulation of Antioxidant Genes Is Dependent on the Formation of a FoxO3a/PGC-1# Complex. Antioxid Redox Signal, 2013 19(13): 1507-21.Martínez-Ruiz A; Araújo IM,; Izquierdo-Álvarez A,; Hernansanz-Agustín P; Lamas S,; Serrador JM. Specificity in S-Nitrosylation: A Short-Range Mechanism for NO Signaling?. Antioxid Redox Signal 
  • Laares, D., Busnadiego, O., García-Fernández, R.A., Lamas, S, and Rodríguez-Pascual, F. (2012) Adenoviral gene transfer of endothelin-1 in the lung induces pulmonary fibrosis through the activation of focal adhesion kinase. Am J Respir Cell Mol Biol. 47(6):834-42.
  • Martínez-Acedo, P., Núñez, E., Gómez, F.J., Moreno, M., Ramos, E., Izquierdo-Álvarez, A., Miró-Casas, E., Mesa, R., Rodríguez, P., Martínez-Ruiz, A., Dorado, D.G., Lamas, S, and Vázquez, J. (2012) A novel strategy for global analysis of the dynamic thiol redox proteome. Mol Cell Proteomics. 11(9):800-13.
  • Rodríguez-Pascual, F., Busnadiego, O., Lagares, D., and Lamas, S. (2011) Role of endothelin in the cardiovascular system. Pharmacol Res, 63(6):463-472.
  • Martínez-Ruiz, A., Cadenas, S., and Lamas, S. (2011) Nitric oxide signaling: classical, less classical, and nonclassical mechanisms. Free Radic Biol Med. 51(1):17-29.
  • Loureiro, J., Aguilera, A., Selgas, R., Sandoval, P., Albar-Vizcaíno, P., Pérez-Lozano, M.L., Ruiz-Carpio, V., Majano, P.L., Lamas, S., Rodríguez-Pascual, F., Borras-Cuesta, F., Dotor, J., and López-Cabrera, M. (2011) Blocking TGF-β1 protects the peritoneal membrane from dialysate-induced damage. J Am Soc Nephrol 22(9):1682-1695.

 


Doctoral Thesis:

M. Cristina  Espinosa Diez (2015). Papel de la g-glutamilcistein ligasa en modelos de daño vascular y fibrótico e implicación de miR-433 en la sintesis de  glutation. Director: Santiago Lamas

M. Ángeles Higueras López (2014). Fisiología y Fisiopatología de DLK-1 en el Endotelio Vascular. Universidad Complutense de Madrid. Directores: Santiago Lamas y Patricia Rodríguez

Rosa Bretón Romero (2013). Redox Signaling Responses to Laminar Shear Stress in vascular endothelial cells. Universidad Autónoma de Madrid. Director:Santiago Lamas

David Lagares Salto (2012) Implicaciones Fisiopatológicas y Terapeuticas del eje TGF-beta/ET-1 y la Quinasa de Adhesión Focal en los procesos Fibróticos. Universidad Autónoma de Madrid. Directores: Santiago Lamas Peláez y Fernando Rodríguez Pascual.


Patents:

European Application "Compounds for prevention and/or treatment of fibrotic diseases" Application No/Patent No 14382239.3-1401

International application  201031547 “Uso de Dlk1 como inhibidor de angiogénesis”, Dec 2011.


 Other activities:

.Organización de actividades I + D:

  • "Redox signaling and oxidative stress in health and disease IV Spanish and Portuguese meeting on free radicals" Valencia. Junio 2012
  • "Workshop on Gasotransmitters in health and disease" Madrid. Enero 2012
  • "XVII Simposio Internacional del Instituto "Reina Sofía" de Investigaciones Nefrológicas". Noviembre 2011
  • "Current Trends In Biomedicine. Molecular and Cellular Bases of Redox Signaling and Oxidative Stress: Implications in Biomedicine". Universidad Internacional de Andalucía. Simposium Internacional Baeza. Noviembre 2011
  • Curso de Verano "La fibrosis tisular en la enfermedad humana". Fundación General de la Universidad de Álcala de Henares. Septiembre 2012.

 

 Editor asociado  de la revista Redox Biology http://www.journals.elsevier.com/redox-biology/