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Immunonano-Lipocarrier-Mediated Liver Sinusoidal Endothelial Cell-Specific RUNX1 Inhibition Impedes Immune Cell Infiltration and Hepatic Inflammation in Murine Model of NASH.
Tripathi, Dinesh Mani; Rohilla, Sumati; Kaur, Impreet; Siddiqui, Hamda; Rawal, Preety; Juneja, Pinky; Kumar, Vikash; Kumari, Anupama; Naidu, Vegi Ganga Modi; Ramakrishna, Seeram; Banerjee, Subham; Puria, Rekha; Sarin, Shiv K; Kaur, Savneet.
Afiliación
  • Tripathi DM; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi 110070, India.
  • Rohilla S; School of Biotechnology, Gautam Buddha University, Greater Noida 201312, India.
  • Kaur I; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi 110070, India.
  • Siddiqui H; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi 110070, India.
  • Rawal P; School of Biotechnology, Gautam Buddha University, Greater Noida 201312, India.
  • Juneja P; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi 110070, India.
  • Kumar V; Stem Cell Biology Laboratory, National Institute of Immunology, New Delhi 110067, India.
  • Kumari A; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi 110070, India.
  • Naidu VGM; Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Guwahati 781122, India.
  • Ramakrishna S; Department of Mechanical Engineering, National University of Singapore, Singapore 117575, Singapore.
  • Banerjee S; Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Guwahati 781122, India.
  • Puria R; School of Biotechnology, Gautam Buddha University, Greater Noida 201312, India.
  • Sarin SK; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi 110070, India.
  • Kaur S; Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi 110070, India.
Int J Mol Sci ; 22(16)2021 Aug 06.
Article en En | MEDLINE | ID: mdl-34445195
BACKGROUND: Runt-related transcription factor (RUNX1) regulates inflammation in non-alcoholic steatohepatitis (NASH). METHODS: We performed in vivo targeted silencing of the RUNX1 gene in liver sinusoidal endothelial cells (LSECs) by using vegfr3 antibody tagged immunonano-lipocarriers encapsulated RUNX1 siRNA (RUNX1 siRNA) in murine models of methionine choline deficient (MCD) diet-induced NASH. MCD mice given nanolipocarriers-encapsulated negative siRNA were vehicle, and mice with standard diet were controls. RESULTS: Liver RUNX1 expression was increased in the LSECs of MCD mice in comparison to controls. RUNX1 protein expression was decreased by 40% in CD31-positive LSECs of RUNX1 siRNA mice in comparison to vehicle, resulting in the downregulation of adhesion molecules, ICAM1 expression, and VCAM1 expression in LSECs. There was a marked decrease in infiltrated T cells and myeloid cells along with reduced inflammatory cytokines in the liver of RUNX1 siRNA mice as compared to that observed in the vehicle. CONCLUSIONS: In vivo LSEC-specific silencing of RUNX1 using immunonano-lipocarriers encapsulated siRNA effectively reduces its expression of adhesion molecules, infiltrate on of immune cells in liver, and inflammation in NASH.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Interferente Pequeño / Interferencia de ARN / Subunidad alfa 2 del Factor de Unión al Sitio Principal / Enfermedad del Hígado Graso no Alcohólico / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: India Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Interferente Pequeño / Interferencia de ARN / Subunidad alfa 2 del Factor de Unión al Sitio Principal / Enfermedad del Hígado Graso no Alcohólico / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: India Pais de publicación: Suiza