Extracellular vesicles and microRNAs in metabolic dysfunction-associated steatotic liver disease: from steatosis to hepatocellular carcinoma

Authors

  • Melina Keingeski Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0002-8001-3017
  • Larisse Longo Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0002-4453-7227
  • Anelise da Silva Pinto Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0003-1467-3065
  • Bruno de Souza Basso Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0001-5331-6787
  • Thalia Michele Vier Schmitz Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0009-0001-3945-0821
  • Vitória Brum da Silva Nunes Laboratory of Cancer Immunobiochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Graduate Program in Biological Sciences: Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0002-5651-8912
  • Juliete Nathali Scholl Laboratory of Cancer Immunobiochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Graduate Program in Biological Sciences: Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0002-9509-2010
  • Camila Kehl Dias Laboratory of Cancer Immunobiochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Graduate Program in Biological Sciences: Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0002-1898-1420
  • Fabrício Figueiró Laboratory of Cancer Immunobiochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Graduate Program in Biological Sciences: Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0003-0899-6407
  • Danieli Rosane Dallemole Graduate Program in Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0002-3860-7487
  • Adriana Roffin Pohlmann Graduate Program in Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0001-5222-1807
  • Isabel Veloso Pereira Laboratório de Investigação Médica (LIM07) do Hospital das Clínicas, da Faculdade de Medicina da Universidade de São Paulo, SP, Brazil; Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo-SP, Brazil https://orcid.org/0000-0002-3439-1658
  • Jose Tadeu Stefano Laboratório de Investigação Médica (LIM07) do Hospital das Clínicas, da Faculdade de Medicina da Universidade de São Paulo, SP, Brazil; Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo-SP, Brazil https://orcid.org/0000-0002-0218-1920
  • José Eduardo Vargas Laboratory of Inflammatory and Neoplastic Cells, Department of Cell Biology, Section of Biological Sciences, Universidade Federal do Parana, Curitiba, Brazil https://orcid.org/0000-0002-7729-5738
  • Patrícia Luciana da Costa Lopez Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil https://orcid.org/0000-0002-7700-497X
  • Claudia P. Oliveira Laboratório de Investigação Médica (LIM07) do Hospital das Clínicas, da Faculdade de Medicina da Universidade de São Paulo, SP, Brazil; Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo-SP, Brazil; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, CNPq researcher https://orcid.org/0000-0002-2848-417X
  • Juan Pablo Arab Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA; Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile https://orcid.org/0000-0002-8561-396X
  • Mário Reis Álvares-da-Silva Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, n° 2350/ sala 2033, 2° andar Santa Cecília, Porto Alegre 90035-903, Rio Grande do Sul, Brazil, E-mail: marioreis@live.com https://orcid.org/0000-0002-5001-246X
  • Carolina Uribe-Cruz Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, n° 2350, 2° andar Santa Cecília, Porto Alegre 90035-903, Rio Grande do Sul, Brazil, E-mail: carolinaurib10@yahoo.com.ar https://orcid.org/0000-0002-0526-3067

DOI:

https://doi.org/10.17179/excli2025-8710

Keywords:

Cirrhosis, extracellular vesicles, hepatocellular carcinoma (HCC), Metabolic-dysfunction associated Steatotic Liver Disease (MASLD);, metabolic dysfunction-associated steatohepatitis, microRNAs

Abstract

Extracellular vesicles (EVs) and microRNAs, involved in intercellular communication, have emerged as potential biomarkers in liver diseases. This study aimed to evaluate EV characteristics and microRNA transport across the full spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD). 168 patients with MASLD and 50 controls were recruited. Biochemical and clinical variables were evaluated. EVs were isolated from serum and characterized by nanoparticle tracking analysis, flow cytometry, and Western blotting. Using MiRWalk 3.0 and the TarPmiR algorithm, candidate EV-associated microRNAs related to MASLD were identified. The expression of miR-4758, miR-188, miR-1226, and miR-122, was evaluated in EVs and serum. EV size and concentration varied significantly across disease stages (p<0.001 and p<0.05, respectively), with early MASLD dominated by exosome, and later stages showing a shift toward microvesicles. In MASLD patients, interestingly, miR-122 was lower in EVs compared to serum (p<0.05). In steatosis, it was higher in serum than EVs (p<0.05), without significant differences in later stages. miR-122 in EVs increased in association with GGT and cholesterol, and decreased with elevated creatinine. Serum miR-122 was also elevated in patients with high cholesterol. In MASLD miR-4758 was higher in EVs than in serum (p<0.05), expressed in steatosis and cirrhosis (p<0.05), suggesting it is a good disease marker, and detected exclusively in serum in HCC (p<0.05). miR-4758–EVs increased with high glucose. MiR-188 and miR-1226 were exclusively expressed in serum (p<0.05), and miR-1226 was elevated in patients with high cholesterol. EV size was reduced in individuals with high triglycerides and albumin, suggesting interaction between EVs, biochemical parameters and disease stage. These findings suggest that microRNA expression and transport in EVs and serum vary across MASLD stages and associate with key biochemical parameters, supporting the clinical value of jointly assessing both compartments as potential biomarkers to distinguish early disease from advanced stages such as HCC.

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Published

2025-10-23

How to Cite

Keingeski, M., Longo, L., da Silva Pinto, A., de Souza Basso, B., Vier Schmitz, T. M., Brum da Silva Nunes, V., … Uribe-Cruz, C. (2025). Extracellular vesicles and microRNAs in metabolic dysfunction-associated steatotic liver disease: from steatosis to hepatocellular carcinoma. EXCLI Journal, 24, 1438–1455. https://doi.org/10.17179/excli2025-8710

Issue

Vol. 24 (2025)

Section

Original articles

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Copyright (c) 2025 Melina Keingeski, Larisse Longo, Anelise da Silva Pinto, Bruno de Souza Basso, Thalia Michele Vier Schmitz, Vitória Brum da Silva Nunes, Juliete Nathali Scholl, Camila Kehl Dias, Fabrício Figueiró, Danieli Rosane Dallemole, Adriana Roffin Pohlmann, Isabel Veloso Pereira, Jose Tadeu Stefano, José Eduardo Vargas, Patrícia Luciana da Costa Lopez, Claudia P. Oliveira, Juan Pablo Arab, Mário Reis Álvares-da-Silva, Carolina Uribe-Cruz

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