title: Transplantation of bone marrow-derived MSCs improves renal function and Na++K+-ATPase activity in rats with renovascular hypertension.
abstract: Renovascular hypertension (RVH) is a progressive disease, leading to chronic kidney disease when untreated and no specific treatment is available. Therefore, development of new therapeutic modalities is imperative. RVH is triggered by renal artery stenosis and subsequent renin-angiotensin-aldosterone system activation; it can be experimentally induced by the 2 Kidneys-1 Clip (2K1C) model. This study investigates the therapeutic potential of renal subcapsular mesenchymal stem cell (MSC) infusion in 2K1C rats. Renal morphological and functional changes were analyzed, including Na++K+-ATPase activity and expression, renin angiotensin-converting enzyme (ACE) and angiotensin-II type 1 (AT1R) and type 2 (AT2R) receptors expression. 2K1C rats developed hypertension accompanied by renin upregulation (clipped kidney) and renal Na++K+-ATPase activity and expression reduction. MSC therapy decreased systolic blood pressure, renin, ACE, and AT1R, upregulated AT2R and podocin expression and restored renal Na++K+-ATPase activity and expression. In addition, MSC improved renal morphology, reduced fibrosis and TGF-β expression in the clipped kidney, decreased proteinuria and restored protein plasma levels. In conclusion, transplantation into a renal subcapsule is an efficient route and MSC is a good candidate for cell therapy, which may represent an interesting approach for chronic kidney disease treatment.
authors.affiliation: Histology and Embryology Department, Stem Cell Research Laboratory, State University of Rio de Janeiro, Av. Professor Manuel de Abreu, 444, Vila Isabel, CEP: 20.551-17, Rio de Janeiro, RJ, Brazil. rafaellelira@gmail.com.
authors.forename: Rafaelle
authors.initials: R
authors.lastname: Lira
authors.affiliation: Histology and Embryology Department, Stem Cell Research Laboratory, State University of Rio de Janeiro, Av. Professor Manuel de Abreu, 444, Vila Isabel, CEP: 20.551-17, Rio de Janeiro, RJ, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Oliveira
authors.affiliation: Histology and Embryology Department, Stem Cell Research Laboratory, State University of Rio de Janeiro, Av. Professor Manuel de Abreu, 444, Vila Isabel, CEP: 20.551-17, Rio de Janeiro, RJ, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: Martins
authors.affiliation: Histology and Embryology Department, Stem Cell Research Laboratory, State University of Rio de Janeiro, Av. Professor Manuel de Abreu, 444, Vila Isabel, CEP: 20.551-17, Rio de Janeiro, RJ, Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Silva
authors.affiliation: Histology and Embryology Department, Stem Cell Research Laboratory, State University of Rio de Janeiro, Av. Professor Manuel de Abreu, 444, Vila Isabel, CEP: 20.551-17, Rio de Janeiro, RJ, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Carvalho
authors.affiliation: Histology and Embryology Department, Stem Cell Research Laboratory, State University of Rio de Janeiro, Av. Professor Manuel de Abreu, 444, Vila Isabel, CEP: 20.551-17, Rio de Janeiro, RJ, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Stumbo
authors.affiliation: Histology and Embryology Department, Stem Cell Research Laboratory, State University of Rio de Janeiro, Av. Professor Manuel de Abreu, 444, Vila Isabel, CEP: 20.551-17, Rio de Janeiro, RJ, Brazil.
authors.forename: Erika
authors.initials: E
authors.lastname: Cortez
authors.affiliation: Federal University of Rio de Janeiro, Macaé - Av. Aloízio da Silva Gomes 50, Granja dos Cavaleiros, Macaé, Rio de Janeiro, Brazil.
authors.forename: Karine
authors.initials: K
authors.lastname: Verdoorn
authors.affiliation: Federal University of Rio de Janeiro, Institute of Biophysics Carlos Chagas Filho, Av. Carlos Chagas Filho, 373, Ilha do Fundão, Rio de Janeiro, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Einicker-Lamas
authors.affiliation: Histology and Embryology Department, Stem Cell Research Laboratory, State University of Rio de Janeiro, Av. Professor Manuel de Abreu, 444, Vila Isabel, CEP: 20.551-17, Rio de Janeiro, RJ, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Thole
authors.affiliation: Histology and Embryology Department, Stem Cell Research Laboratory, State University of Rio de Janeiro, Av. Professor Manuel de Abreu, 444, Vila Isabel, CEP: 20.551-17, Rio de Janeiro, RJ, Brazil.
authors.forename: Laís
authors.initials: L
authors.lastname: de Carvalho
mesh_terms: D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure; D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation; D058948:Cell Tracking; D003094:Collagen / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012083:Renin; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013599:Systole; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D051028:bcl-2-Associated X Protein; D049452:Green Fluorescent Proteins; D003094:Collagen; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D000254:Sodium-Potassium-Exchanging ATPase
keywords: 2-Kidney 1-Clip; Cell therapy; Chronic kidney disease; Mesenchymal stem cell; Na++K+-ATPase; Renovascular hypertension