Transplantation of bone marrow-derived MSCs improves renal function and Na ++K +-ATPase activity in rats with renovascular hypertension

Cell Tissue Res. 2017 Aug;369(2):287-301. doi: 10.1007/s00441-017-2602-3. Epub 2017 Apr 3.

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.

Keywords: 2-Kidney 1-Clip; Cell therapy; Chronic kidney disease; Mesenchymal stem cell; Na++K+-ATPase; Renovascular hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blood Pressure
  • Bone Marrow Cells / cytology*
  • Cell Proliferation
  • Cell Tracking
  • Collagen / metabolism
  • Green Fluorescent Proteins / metabolism
  • Hypertension, Renovascular / enzymology*
  • Hypertension, Renovascular / pathology
  • Hypertension, Renovascular / physiopathology*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kidney / enzymology*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / physiopathology*
  • Kidney Function Tests
  • Male
  • Membrane Proteins / metabolism
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Peptidyl-Dipeptidase A / metabolism
  • Rats, Wistar
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Renin
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Systole
  • Up-Regulation
  • bcl-2-Associated X Protein / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • bcl-2-Associated X Protein
  • Green Fluorescent Proteins
  • Collagen
  • Peptidyl-Dipeptidase A
  • Renin
  • Sodium-Potassium-Exchanging ATPase