Hypertension is a long-term condition that can increase organ susceptibility to insults and lead to severe complications such as chronic kidney disease (CKD). Extracellular vesicles (EVs) are cell-derived membrane structures that participate in cell-cell communication by exporting encapsulated molecules to target cells, regulating physiological and pathological processes. We here demonstrate that multiple administration of EVs from adipose-derived mesenchymal stromal cells (ASC-EVs) in deoxycorticosterone acetate (DOCA)-salt hypertensive model can protect renal tissue by maintaining its filtration capacity. Indeed, ASC-EVs downregulated the pro-inflammatory molecules monocyte chemoattracting protein-1 (MCP-1) and plasminogen activating inhibitor-1 (PAI1) and reduced recruitment of macrophages in the kidney. Moreover, ASC-EVs prevented cardiac tissue fibrosis and maintained blood pressure within normal levels, thus demonstrating their multiple favorable effects in different organs. By applying microRNA (miRNA) microarray profile of the kidney of DOCA-salt rats, we identified a selective miRNA signature associated with epithelial-mesenchymal transition (EMT). One of the key pathways found was the axis miR-200-TGF-β, that was significantly altered by EV administration, thereby affecting the EMT signaling and preventing renal inflammatory response and fibrosis development. Our results indicate that EVs can be a potent therapeutic tool for the treatment of hypertension-induced CKD in cardio-renal syndrome.

Adipose mesenchymal cells-derived EVs alleviate DOCA-salt-induced hypertension by promoting cardio-renal protection / R.S. Lindoso, J.A. Lopes, R. Binato, E. Abdelhay, C.M. Takiya, K.R. de Miranda, L.S. Lara, A. Viola, B. Bussolati, A. Vieyra, F. Collino. - In: MOLECULAR THERAPY. METHODS & CLINICAL DEVELOPMENT. - ISSN 2329-0501. - 16:(2020 Mar 13), pp. 63-77. [10.1016/j.omtm.2019.11.002]

Adipose mesenchymal cells-derived EVs alleviate DOCA-salt-induced hypertension by promoting cardio-renal protection

F. Collino
2020

Abstract

Hypertension is a long-term condition that can increase organ susceptibility to insults and lead to severe complications such as chronic kidney disease (CKD). Extracellular vesicles (EVs) are cell-derived membrane structures that participate in cell-cell communication by exporting encapsulated molecules to target cells, regulating physiological and pathological processes. We here demonstrate that multiple administration of EVs from adipose-derived mesenchymal stromal cells (ASC-EVs) in deoxycorticosterone acetate (DOCA)-salt hypertensive model can protect renal tissue by maintaining its filtration capacity. Indeed, ASC-EVs downregulated the pro-inflammatory molecules monocyte chemoattracting protein-1 (MCP-1) and plasminogen activating inhibitor-1 (PAI1) and reduced recruitment of macrophages in the kidney. Moreover, ASC-EVs prevented cardiac tissue fibrosis and maintained blood pressure within normal levels, thus demonstrating their multiple favorable effects in different organs. By applying microRNA (miRNA) microarray profile of the kidney of DOCA-salt rats, we identified a selective miRNA signature associated with epithelial-mesenchymal transition (EMT). One of the key pathways found was the axis miR-200-TGF-β, that was significantly altered by EV administration, thereby affecting the EMT signaling and preventing renal inflammatory response and fibrosis development. Our results indicate that EVs can be a potent therapeutic tool for the treatment of hypertension-induced CKD in cardio-renal syndrome.
cardio-renal syndrome; chronic kidney disease; epithelial-mesenchymal transition; extracellular vesicles; hypertension; microRNAs
Settore MED/05 - Patologia Clinica
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
Settore MED/14 - Nefrologia
15-ott-2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/853261
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