Calcitonin induces connective tissue growth factor through ERK1/2 signaling in renal tubular cells

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.

Calcitonin induces connective tissue growth factor through ERK1/2 signaling in renal tubular cells

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.

Regulation of the renal proximal tubule second sodium pump by angiotensins

For several years it was believed that angiotensin II (Ang II) alone mediated the effects of the renin-angiotensin system. However, it has been observed that other peptides of this system, such as angiotensin-(1-7) (Ang-(1-7)), present biological activity. The effect of Ang II and Ang-(1-7) on renal sodium excretion has been associated, at least in part, with modulation of proximal tubule sodium reabsorption. In the present review, we discuss the evidence for the involvement of Na+-ATPase, called the second sodium pump, as a target for the actions of these compounds in the regulation of proximal tubule sodium reabsorption

Effect of bafilomycin on proximal bicarbonate absorption in the rat

To evaluate the relative importance of the V-type H(+)-ATPase in proximal bicarbonate reabsorption in vivo, proximal tubules of male and female Wistar rats (180 to 260 g) were perfused with bicarbonate-Ringer solution with and without the addition of 2 microM bafilomycin A1. Bafilomycin significantly increased stationary pH from 6.75 +/- 0.05 (N = 39) to 6.86 +/- 0.03 (N = 82), the stationary concentration of bicarbonate from 5.24 +/- 0.62 to 6.33 +/- 0.46 mM and the half-time of acidification from 3.72 +/- 0.22 to 4.65 +/- 0.25 s, and significantly decreased net bicarbonate reabsorption from 3.17 +/- 0.21 to 2.55 +/- 0.15 nmol s-1 cm-2, that is, by 20 per cent . Since bafilomycin is considered to be a specific inhibitor for V-type H(+)-ATPase, these data establish 1) the existence of this type of transport in the rat proximal tubule and 2) that approximately a fifth of the total proximal bicarbonate reabsorption is due to this mechanism of transport

Interactions of the regulatory ligands Mg2+ and MgATP2- with the renal plasma membrane Ca(2+)-ATPase: effects of osmolytes that stabilize or destabilize protein structure

In this report we analyze the kinetics of activation of the plasma membrane Ca(2+)-ATPase from kidney proximal tubules by the regulatory ligands Mg2+ and MgATP2-, and we examine modifications in the effects of these ligands that are promoted by organic solutes of natural occurrence that stabilize or destabilize protein structure and function. The solutes tested were trimethylamine-N-oxide (TMA-O), sucrose and urea. TMA-O and sucrose were chosen as representative of the different methylamines and polyols, respectively, that accumulate in living organisms. The results lead to the conclusion that free Mg2+ and the MgATP2- complex both activate the rate-determining E2-->E1 transition during the catalytic cycle of the enzyme, by binding to nonidentical and independent regulatory sites. They also indicate that TMA-O, sucrose and urea not only promote global modifications in the enzyme structure, but also modify specific interactions of the ligands Mg2+ and MgATP2- at their regulatory sites