J. Pharm. Pharmacogn. Res., vol. 12, no. 3, pp. 586-593, May-Jun 2024.
DOI: https://doi.org/10.56499/jppres23.1937_12.3.586
Original article
Colchicine modulates TIMP1, MMP1, and pMAP4 expression to enhance extracellular matrix degradation in 3T3 fibroblast-mediated myocardial infarction
[Colchicina modula la expresión de TIMP1, MMP1 y pMAP4 para potenciar la degradación de la matriz extracelular en el infarto de miocardio mediado por fibroblastos 3T3]
Saskia Dyah Handari1,2,3*, Mohammad Saifur Rahman3, Djanggan Sargowo4, Aulanni’am Aulanni’am5, Bayu Lestari6, Delvac Oceandy6
1Doctoral Program of Medical Science, Brawijaya University, Malang, East Java, Indonesia.
2Medical Faculty, Ciputra University Surabaya, Indonesia.
3Department of Cardiology and Cardiovascular Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, Indonesia.
4Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, Indonesia.
5Department of Chemistry, Faculty of Sciences, Universitas Brawijaya, Malang, Indonesia.
6Division of Cardiovascular Sciences, University of Manchester, United Kingdom.
*E-mail: saskia.handari@ub.ac.id, saskiahandari@outlook.com
Abstract
Context: Cardiovascular disease is a leading cause of mortality worldwide. Following acute myocardial infarction (AMI), cardiac cells release many cytokines and proteolytic enzymes that regulate the extracellular matrix (ECM), including matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and phosphorylated microtubule-associated protein 4 (Phospho/pMAP4).
Aims: To analyze the role of colchicine in ECM regulation post-ischemic in cell line culture towards MMPs, TIMPs, and pMAP4.
Methods: This in vitro experimental study was conducted on the 3T3 fibroblast cell line subjected to hypoxic conditions (CoCl2 treatment) and compared with 3T3 cells experiencing hypoxia/ischemic and colchicine treatment. MMP-1, TIMP-1, and pMAP4 expression were measured using flow cytometry. Data analysis was performed using One-Way ANOVA with a 95% confidence level.
Results: Treatment with colchicine in the 3T3 fibroblast cell culture regulated the extracellular matrix by increasing TIMP-1 expression and reducing MMP-1 and pMAP4 expression (p<0.0001) following ischemic conditions induced by CoCl2.
Conclusions: Colchicine effectively mitigates ECM degradation by enhancing TIMP-1 expression and inhibiting MMP-1 activity and pMAP4 expression post-ischemic conditions.
Keywords: cell line; colchicine; extracellular matrix; ischemia.
Resumen
Contexto: Las enfermedades cardiovasculares son una de las principales causas de mortalidad en todo el mundo. Tras un infarto agudo de miocardio (IAM), las células cardiacas liberan muchas citocinas y enzimas proteolíticas que regulan la matriz extracelular (MEC), incluidas las metaloproteinasas de matriz (MMP), los inhibidores tisulares de las metaloproteinasas (TIMP) y la proteína 4 fosforilada asociada a microtúbulos (Phospho/pMAP4).
Objetivos: Analizar el papel de la colchicina en la regulación de la MEC post-isquémica en cultivos de líneas celulares en relación con las MMPs, TIMPs y pMAP4.
Métodos: Este estudio experimental in vitro se realizó en la línea celular de fibroblastos 3T3 sometida a condiciones de hipoxia (tratamiento con CoCl2) y se comparó con células 3T3 que experimentaron hipoxia/isquemia y tratamiento con colchicina. La expresión de MMP-1, TIMP-1 y pMAP4 se midió mediante citometría de flujo. El análisis de los datos se realizó mediante ANOVA unidireccional con un nivel de confianza del 95%.
Resultados: El tratamiento con colchicina en el cultivo celular de fibroblastos 3T3 reguló la matriz extracelular aumentando la expresión de TIMP-1 y reduciendo la expresión de MMP-1 y pMAP4 (p<0,0001) tras condiciones isquémicas inducidas por CoCl2.
Conclusiones: La colchicina mitiga eficazmente la degradación de la MEC aumentando la expresión de TIMP-1 e inhibiendo la actividad de MMP-1 y la expresión de pMAP4 tras condiciones de isquemia.
Palabras Clave: línea celular; colchicina; matriz extracelular; isquemia.
Citation Format: Dyah Handari S, Saifur Rohman M, Sargowo D, Aulanni’am A, Lestari B, Oceandy D (2024) Colchicine modulates TIMP1, MMP1, and pMAP4 expression to enhance extracellular matrix degradation in 3T3 fibroblast-mediated myocardial infarction. J Pharm Pharmacogn Res 12(3): 586–593. https://doi.org/10.56499/jppres23.1937_12.3.586
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