Entrecruzamiento de Colágeno y Resistencia a la Degradación: Análisis Fisiopatológico de la Ineficacia Clínica de los Anticuerpos Anti-LOXL2

Enrique Xavier Rodriguez-Burnham; Danna Carolina Cruz-Zapata; David Alejandro Dueñas-Lliguichuzca; Maritza Anamilet Carriel-Rodríguez

Autores/as

Rodriguez-Burnham Enrique Xavier Universidad de Guayaquil. Guayaquil, Ecuador. https://orcid.org/0000-0002-4275-3831
Cruz-Zapata Danna Carolina Universidad de Guayaquil. Guayaquil, Ecuador. https://orcid.org/0009-0003-8413-2958
Dueñas-Lliguichuzca David Alejandro Universidad de Guayaquil. Guayaquil, Ecuador. https://orcid.org/0009-0003-1534-7672
Carriel-Rodríguez Maritza Anamilet Universidad de Guayaquil. Guayaquil, Ecuador. https://orcid.org/0009-0002-4568-092X

Palabras clave:

Cirrosis hepática, fibrosis experimental, lisil oxidasa 2, terapéutica antifibrótica, modelo murino

Resumen

DOI: https://doi.org/10.46296/gt.v9i18.0404

Resumen

La cirrosis hepática es una enfermedad progresiva caracterizada por la acumulación de matriz extracelular y colágeno. La enzima LOXL2 contribuye a la estabilización de la fibrosis y, aunque su inhibición ha mostrado resultados favorables en modelos murinos, no ha demostrado beneficios clínicos significativos en humanos. Se realizó una revisión narrativa bajo el marco SALSA, analizando 28 artículos publicados entre 2020 y 2026, obtenidos de PubMed/MEDLINE y Google Académico. Las fuentes fueron seleccionadas, evaluadas y sintetizadas según su relevancia. La fibrosis hepática resulta de una interacción compleja entre inflamación, muerte celular y acumulación de matriz extracelular. El fracaso del anticuerpo anti-LOXL2 se relaciona con diferencias entre los modelos murinos y humanos, especialmente en la respuesta inmunitaria, actividad enzimática y características de la matriz fibrótica. Por ello, la inhibición aislada de LOXL2 resulta insuficiente, siendo necesario desarrollar estrategias combinadas que favorezcan la degradación de la fibrosis y modulen el microambiente hepático. Esta revisión analiza las causas de aquella discrepancia.

Palabras claves: Cirrosis hepática, fibrosis experimental, lisil oxidasa 2, terapéutica antifibrótica, modelo murino.

Abstract

Liver cirrhosis is a progressive disease characterized by the accumulation of extracellular matrix and collagen. The LOXL2 enzyme contributes to the stabilization of fibrosis, and although its inhibition has shown favorable results in murine models, it has not demonstrated significant clinical benefits in humans. A narrative review was conducted using the SALSA framework, analyzing 28 articles published between 2020 and 2026, obtained from PubMed/MEDLINE and Google Scholar. The sources were selected, assessed, and synthesized according to their relevance. Liver fibrosis results from a complex interaction between inflammation, cell death, and extracellular matrix accumulation. The failure of anti-LOXL2 antibodies is related to differences between murine and human models, especially in the immune response, enzyme activity, and characteristics of the fibrotic matrix. Therefore, isolated inhibition of LOXL2 is insufficient, making it necessary to develop combined strategies that promote fibrosis degradation and modulate the hepatic microenvironment. This review analyzes the causes of this discrepancy.

Keywords: Liver cirrhosis, experimental fibrosis, lysyl oxidase 2, antifibrotic therapy, murine model.

Información del manuscrito:
Fecha de recepción: 14 de julio de 2026.
Fecha de aceptación: 21 de septiembre de 2026.
Fecha de publicación: 20 de octubre de 2026.

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