Proteomic Analysis Reveals Key Proteins in Extracellular Vesicles Cargo Associated with Idiopathic Pulmonary Fibrosis In Vitro
Juan Manuel Velázquez-Enríquez,
Jovito Cesar Santos-Álvarez,
Alma Aurora Ramírez-Hernández,
Edilburga Reyes-Jiménez,
Armando López-Martínez,
Socorro Pina-Canseco,
Sergio Roberto Aguilar-Ruiz,
María de los Ángeles Romero-Tlalolini,
Luis Castro-Sánchez,
Jaime Arellanes-Robledo,
Verónica Rocío Vásquez-Garzón,
Rafael Baltiérrez-Hoyos
Affiliations
Juan Manuel Velázquez-Enríquez
Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico
Jovito Cesar Santos-Álvarez
Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico
Alma Aurora Ramírez-Hernández
Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico
Edilburga Reyes-Jiménez
Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico
Armando López-Martínez
Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico
Socorro Pina-Canseco
Centro de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México-Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico
Sergio Roberto Aguilar-Ruiz
Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico
María de los Ángeles Romero-Tlalolini
CONACYT-Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico
Luis Castro-Sánchez
CONACYT-Universidad de Colima, Centro Universitario de Investigaciones Biomédicas “CUIB”, Universidad de colima, Av. 25 de Julio No. 965, Col. Villas San Sebastián, Colima 28045, Colima, Mexico
Jaime Arellanes-Robledo
CONACYT-Instituto Nacional de Medicina Genómica, 14610 Ciudad de México, Mexico
Verónica Rocío Vásquez-Garzón
CONACYT-Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico
Rafael Baltiérrez-Hoyos
CONACYT-Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible, and highly fatal disease. It is characterized by the increased activation of both fibroblast and myofibroblast that results in excessive extracellular matrix (ECM) deposition. Extracellular vesicles (EVs) have been described as key mediators of intercellular communication in various pathologies. However, the role of EVs in the development of IPF remains poorly understood. This study aimed to characterize the differentially expressed proteins contained within EVs cargo derived from the fibroblast cell lines LL97A (IPF-1) and LL29 (IPF-2) isolated from lungs bearing IPF as compared to those derived from the fibroblast cell lines CCD8Lu (NL-1) and CCD19Lu (NL-2) isolated from healthy donors. Isolated EVs were subjected to label-free quantitative proteomic analysis by LC-MS/MS, and as a result, 331 proteins were identified. Differentially expressed proteins were obtained after the pairwise comparison, including all experimental groups. A total of 86 differentially expressed proteins were identified in either one or more comparison groups. Of note, proteins involved in fibrogenic processes, such as tenascin-c (TNC), insulin-like-growth-factor-binding protein 7 (IGFBP7), fibrillin-1 (FBN1), alpha-2 collagen chain (I) (COL1A2), alpha-1 collagen chain (I) (COL1A1), and lysyl oxidase homolog 1 (LOXL1), were identified in EVs cargo isolated from IPF cell lines. Additionally, KEGG pathway enrichment analysis revealed that differentially expressed proteins participate in focal adhesion, PI3K-Akt, and ECM–receptor interaction signaling pathways. In conclusion, our findings reveal that proteins contained within EVs cargo might play key roles during IPF pathogenesis.