Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (6): 988-995.doi: 10.4103/1673-5374.270299

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Type XIX collagen: a promising biomarker from the basement membranes

Ana C. Calvo1, Laura Moreno1, Leticia Moreno1, Janne M. Toivonen1, Raquel Manzano1, Nora Molina1, Miriam de la Torre1, Tresa López1, Francisco J. Miana-Mena1, María J. Muñoz1, Pilar Zaragoza1, Pilar Larrodé2, Alberto García-Redondo3, Rosario Osta1#br#   

  1. 1 Laboratory of Genetics and Biochemistry (LAGENBIO), University of Zaragoza, Faculty of Veterinary Sciences, Instituto de Investigación Sanitaria de Aragón (IIS), IA2, CIBERNED, Zaragoza, Spain
    2 Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
    3 Neurology Department, ALS Unit, CIBERER U-723, Health Research Institute, Madrid, Spain
  • Online:2020-06-15 Published:2020-07-01
  • Contact: Rosario Osta, PhD, osta@unizar.es.
  • Supported by:
    This work was supported by Institutode Salud Carlos III (Grant PI17/00949) and Fondo Europeode Desarrollo Regional (FEDER) “Una manera de hacer Europa” from the European Union, Centrode Investigación Biomédicaen Redsobre Enfermedades Neurodegenerativas (CIBERNED-612), Fundación FEDER (Federación Españolade Enfermedades Raras), Consolidated Groupsfrom Gobiernode Aragón.

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Abstract: Among collagen members in the collagen superfamily, type XIX collagen has raised increasing interest in relation to its structural and biological roles. Type XIX collagen is a Fibril-Associated Collagen with Interrupted Triple helices member, one main subclass of collagens in this superfamily. This collagen contains a triple helix composed of three polypeptide segments aligned in parallel and it is associated with the basement membrane zone in different tissues. The molecular structure of type XIX collagen consists of five collagenous domains, COL1 to COL5, interrupted by six non-collagenous domains, NC1 to NC6. The most relevant domain by which this collagen exerts its biological roles is NC1 domain that can be cleavage enzymatically to release matricryptins, exerting anti-tumor and anti-angiogenic effect in murine and human models of cancer. Under physiological conditions, type XIX collagen expression decreases after birth in different tissues although it is necessary to keep its basal levels, mainly in skeletal muscle and hippocampal and telencephalic interneurons in brain. Notwithstanding, in amyotrophic lateral sclerosis, altered transcript expression levels show a novel biological effect of this collagen beyond its structural role in basement membranes and its anti-tumor and anti-angiogenic properties. Type XIX collagen can exert a compensatory effect to ameliorate the disease progression under neurodegenerative conditions specific to amyotrophic lateral sclerosis in transgenic SOD1G93A mice and amyotrophic lateral sclerosis patients. This novel biological role highlights its nature as prognostic biomarker of disease progression in and as promising therapeutic target, paving the way to a more precise prognosis of amyotrophic lateral sclerosis.

Key words: anti-tumor and anti-angiogenic properties, C1 domain, COL19A1 gene and protein levels, compensatory effect, FACIT collagens, hippocampal interneurons, matricryptins, multiplexins, NC1 domain, regenerative response, skeletal muscle, type XIX collagen