Identification of molecular pathways and protein-protein interactions in adipose tissue-derived mesenchymal stromal cells (ASCs) under physiological oxygen concentration in a diabetic rat model.

Objectives: Adipose tissue-derived mesenchymal stromal cells (ASCs) are useful in cell-based therapy. However, it is well known that diabetes mellitus (DM) alters ASCs' functionality. The majority of studies related to ASCs are developed under non-physiological oxygen conditions.

Hypoxia preconditioning increases the ability of healthy but not diabetic rat-derived adipose stromal/stem cells (ASC) to improve histological lesions of streptozotocin-induced diabetic nephropathy.

Background: Mesenchymal stromal cells (MSC) have demonstrated ability to improve diabetic nephropathy (DN) in experimental models, as well as by improving kidney endogenous progenitor cells proliferation and differentiation. Many studies have demonstrated the effect of hypoxia on MSC improving their functionality but the potential enhancement of the nephroprotective properties of MSC cultured under low oxygen concentration has been explored in few studies, none of them in the context of DN. On the other hand, diabetes is associated with abnormalities in MSCs functionality.

Intramyocardial bone marrow mononuclear cells versus bone marrow-derived and adipose mesenchymal cells in a rat model of dilated cardiomyopathy.

Background: Effects of cell therapy on dilated cardiomyopathy (DCM) have been investigated in pre-clinical models using distinct cellular types in each study. A single study that compares the effectiveness of different cells is lacking.

Methods: We have compared the effects of intramyocardial injection (IMI) of bone marrow (BM)-derived mononuclear cells (MNCs), BM and adipose tissue (AT) mesenchymal stromal cells (BM-MSCs and AT-MSCs) on heart function, histological changes and myocardial ultrastructure in a rat model of DCM.

Darbepoetin-α treatment enhances glomerular regenerative process in the Thy-1 glomerulonephritis model.

Recent studies have demonstrated that erythropoietin (EPO) and its analogs induce cytoprotective effects on many nonerythroid cells. In this study, we examined whether darbepoetin-α might prevent glomerular lesions in the Thy-1.1 model of glomerulonephritis (Thy-1-GN).

Upregulation of parathyroid VDR expression by extracellular calcium is mediated by ERK1/2-MAPK signaling pathway.

We have previously demonstrated that the activation of rat parathyroid calcium-sensing receptor (CaSR) upregulates VDR expression in vivo (Garfia B, Cañadillas S, Luque F, Siendones E, Quesada M, Almadén Y, Aguilera-Tejero E, Rodríguez M. J Am Soc Nephrol 13: 2945-2952, 2002; Rodriguez ME, Almaden Y, Cañadillas S, Canalejo A, Siendones E, Lopez I, Aguilera-Tejero E, Martin D, Rodriguez M. Am J Physiol Renal Physiol 292: F1390-F1395, 2007).

Carbamylated darbepoetin derivative prevents endothelial progenitor cell damage with no effect on angiogenesis.

Erythropoietin (EPO) prevents cell apoptosis induced by oxidative stress. Carbamylated EPO maintains the tissue-protective activities of the unmodified EPO but does not stimulate erythropoiesis. This study evaluates whether carbamylated erythropoietin is as effective as recombinant human erythropoietin in protecting endothelial progenitor cells (EPCs) from apoptosis without stimulating erythropoiesis.

Calcimimetics normalize the phosphate-induced stimulation of PTH secretion in vivo and in vitro.

Background: Hyperphosphatemia is a key pathogenic factor in the development of secondary hyperparathyroidism and precludes its treatment with vitamin D. Calcimimetics are therapeutic drugs demonstrated to lower parathyroid hormone (PTH) levels through an increase in the intracellular calcium of parathyroid cells. The mechanism by which high phosphate levels stimulate PTH secretion is related to its ability to prevent the elevation of intracellular calcium.

Cinacalcet reduces the set point of the PTH-calcium curve.

The calcimimetic cinacalcet increases the sensitivity of the parathyroid calcium-sensing receptor to calcium and therefore should produce a decrease in the set point of the parathyroid hormone (PTH)-calcium curve. For investigation of this hypothesis, nine long-term hemodialysis patients with secondary hyperparathyroidism were given cinacalcet for 2 mo, the dosage was titrated per a protocol based on intact PTH and plasma calcium concentrations. Dialysis against low- and high-calcium (0.

Regulation of parathyroid function in chronic renal failure.

This review summarizes the factors involved in the development of hyperparathyroidism secondary (2nd-HPTH) to chronic kidney disease (CKD). Calcium and calcitriol act on their respective specific parathyroid cell receptors to inhibit parathyroid function. As well as the well-known effect of calcium and calcitriol on parathyroid cell function, there is experimental work that demonstrates that phosphate, changes in pH, PTHrP, estrogens, and some cytokines also have an effect on PTH secretion.

Calcium-sensing receptor expression and parathyroid hormone secretion in hyperplastic parathyroid glands from humans.

In uremic patients, severe parathyroid hyperplasia is associated with reduced parathyroid calcium-sensing receptor (CaR) expression. Thus, in these patients, a high serum Ca concentration may be required to inhibit parathyroid hormone (PTH) secretion. This study compares the magnitude of reduction in CaR expression and the degree of the abnormality in Ca-regulated PTH release in vitro.

Proliferation in hyperplastic human and normal rat parathyroid glands: role of phosphate, calcitriol, and gender.

Background: Parathyroid gland hyperplasia develops in azotemic patients. A phosphate excess and calcitriol deficiency play critical roles in its development. Our goals were to determine whether differences in serum phosphate values at parathyroidectomy (PTX) in hemodialysis patients with refractory hyperparathyroidism: (1) correlated with parathyroid cell proliferation; and (2) affected the antiproliferative response to in vitro calcitriol.

Importance of arachidonic acid as a mediator of parathyroid gland response.

The intracellular signaling mechanisms that mediate the regulation of parathyroid hormone (PTH) secretion by parathyroid glands are becoming increasingly more understood. Extracellular calcium modulates parathyroid function by acting on a G protein-coupled calcium-sensing receptor, which activates the hydrolysis of membrane phospholipids by phospholipases C, D, and A2 to generate intracellular signals. Arachidonic acid (AA) produced by phospholiphase A2 (PLA2) appears to play a crucial role throughout the generation of downstream-oxygenated products.

Regulation of parathyroid vitamin D receptor expression by extracellular calcium.

Low extracellular calcium (Ca) stimulates parathyroid hormone (PTH) secretion and also increases the renal synthesis of calcitriol (CTR), which is known to decrease PTH production. This study began with the hypothesis that the parathyroid cell response to CTR may be modulated by extracellular Ca concentration through an effect on parathyroid cell vitamin D receptor (VDR). In the present study, rat parathyroid glands were incubated in low (0.

Regulation of arachidonic acid production by intracellular calcium in parathyroid cells: effect of extracellular phosphate.

The action of extracellular calcium on the calcium receptor in parathyroid cells results in activation of phospholipase C (PLC), PLD, and PLA(2). The PLA(2)-arachidonic acid (AA) intracellular signaling pathway mediates inhibition of parathyroid hormone (PTH) secretion. In addition, stimulation of the calcium receptor produces increases in intracellular calcium levels.