Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice.

Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice

The Phosphate Transporter PiT1 (Slc20a1) Revealed As a New Essential Gene for Mouse Liver Development

BACKGROUND PiT1 (or SLC20a1) encodes a widely expressed plasma membrane protein functioning as a high-affinity Na(+)-phosphate (Pi) cotransporter. As such, PiT1 is often considered as a ubiquitous supplier of Pi for cellular needs regardless of the lack of experimental data. Although the importance of PiT1 in mineralizing processes have been demonstrated in vitro in osteoblasts, chondrocytes an...

Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice.

Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic (kl/kl) mice, excessive 1,25(OH)2D3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular vol...

25-Hydroxyvitamin D3 1-α-hydroxylase-dependent stimulation of renal klotho expression by spironolactone.

BACKGROUND Klotho, a transmembrane protein, protease and hormone mainly expressed in kidney, is required for the suppression of 1,25(OH)2D3-generating 25-hydroxyvitamin D3 1-alpha-hydroxylase (Cyp27b1) by FGF23. Conversely, 1,25(OH)2D3 stimulates, by activating the vitamin D3 receptor (Vdr), the expression of klotho, thus establishing a negative feedback loop. Klotho protects against renal and ...

Is NaHCO3 an antiaging elixir?

EVOLVING EVIDENCE supports that deviation from normal toward the acid spectrum of the acid-base balance is associated with premature death compared with patients with a normal acidbase status. Patients with nondialysis-dependent chronic kidney disease (CKD) and metabolic acidosis have increased mortality compared with CKD patients without metabolic acidosis (5, 9). Furthermore, the risk for mor...