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Projects. Life and Earth Sciences

Study of the role of PSGL-1 in the control of the development of autoimmune diseases

Lead Researcher:
Ana Carmen Urzainqui Mayayo

Research Centre:
Hospital Universitario de la Princesa. Madrid.

Synopsis: 

Ana Carmen Urzainqui Mayayo

Project objectives:
  1. Study of clinical characteristics and description of the autoimmune disease developed spontaneously in mice lacking PSGL-1.
  2. Study of the evolution of autoimmune diseases developing in mice lacking PSGL-1 as they age.
  3. Study of the contribution of PSGL-1 and its ligands in the development of autoimmune diseases in patients with involvement of the connective tissue (scleroderma), as well as in patients with intestinal inflammatory diseases (colitis ulcerosa, Crohn's disease).

Results

The autoimmune study was undertaken using WT mice lacking PSGL-1 and it was observed that the serum of mice deficient in PSGL-1 presents a complex pattern of auto-antibodies which recognise antigens connected with autoimmune diseases affecting connective tissue (Scl-70, Sm, RNP, Jo-1 and SSA/Ro). At early ages only anti-Scl-70 is detected, while at advanced ages the mice present several circulating antibodies.

A histological study was conducted on skin, skeletal muscle and lung tissues to analyse the involvement of internal organs:

  • Thickening of the dermis was observed due to the accumulation of collagen (a crucial characteristic for the diagnosis of scleroderma) at earlier ages (6 weeks), indicating that the disease is totally established at this age.
  • It was possible to describe how mice deficient in PSGL-1 from the age of three months present a myopathy which causes muscular weakness, with high levels of CK and GOT in serum. This type of myopathy is very common in patients with scleroderma.
  • The mice deficient in PSGL-1 were seen to present renal problems at the age of three months, with almost 40% of glomerules affected. Analysis of the serum in these mice indicates that the levels of creatinin and urea in serum are higher in mice that are deficient in PSGL-1 than is the case in WT mice, while the level of albumin is lower. They also present problems with proteinuria and haematuria after the age of 18 months. The results correspond to serious renal involvement, very common in patients with systemic sclerosis.
  • Histological analysis of the lung indicates the presence of interstitial infiltrates of leukocytes in 10% of the mice deficient in PSGL-1 at an early age, while this percentage rises to 60% in mice older than one year, in which it is also possible to observe a point of fibrosis. Interstitial pneumonia is common in patients with scleroderma. These lung lesions, with loss of structure, lead to vascular problems such as arterial hypertension in the lung, which is currently the main cause of death in patients with systemic sclerosis.

Ana Carmen Urzainqui Mayayo

  • Degree: Biology. University of Navarre (1980).
  • Doctorate: Biology, Autonomous University, Madrid (1987). She worked on polio virus and African swine plague virus under the direction of Dr. Luis Carrasco Llamas.
  • Postdoctoral Research Activity in the USA:
    • Massachusetts Institute of Technology (MIT). Scholarship from the MEC (March 1989-Sept 1990). Plant-microbe interaction, nitrogen fixing.
    • University of North Carolina at Chapel Hill. MEC scholarship and Visiting Research Associate (Sept 1990-April 1992). Study of the role of absciscic acid in plants.
    • During this stage she started her training in plants, undertaking studies in genetics and molecular biology.
  • Postdoctoral Research Activity in Spain:
    • Molecular Biology Centre (CBM). Postdoctoral MEC scholarship (1988-March 1989): She took part in projects of Dr. Juan Ortín on flu virus.
    • ETSI for Agricultural Engineering, Microbiology Department, Polytechnic University, Madrid. Postdoctoral Reincorporation Grant (March 1992-June 1993). She worked on projects of Dr. Tomás Ruiz Argüeso on nitrogen fixing and the interaction between plants and pathogens.
    • National Biotechnology Centre (CNB). MEC Postdoctoral Reincorporation Contract (1993-1995). She worked on projects of Dr. Juan Antonio Álvarez on plant-pathogen interaction and on plum pox virus (sharka).
    • CNB, Postdoctoral scholarship associated with a European project (1995-1998). She took part in projects of Dr. Javier Paz-Ares on the myb gene family in plants.
    • Princesa University Hospital, Immunology Dept. Postdoctoral Contract. (1999- 2005). She took part in projects of Dr. Francisco Sánchez Madrid on cell biology of the immune system, through which she gained knowledge in immunology and obtained the results that would lead to her starting her own line of research.
    • During this time, she took part in several research groups and gained a solid and broad training in different scientific areas (microbiology, plants and immunology) together with training in the techniques of genetics, molecular biology, biochemistry and cell biology.
  • Activity as a Miguel Servet Researcher
    • Princesa University Hospital, Immunology Department, Miguel Servet Research Contract at the SNS (ISCIII) (January 2006 - January 2012).
    • During this time she commenced her career as a Principal Investigator. She obtained projects from the Health Research Fund (FIS) and started her own line of research.
  • ISCIII Established Researcher: January 2006.


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