Biomedical subjects

Pierre Meneton

Publications and source records attributed to Pierre Meneton.

23 records · Page 2Linked to original sources

PubMed2003

Renin and kallikrein in connecting tubule of mouse.

BACKGROUND: The observation of renin expression in connecting tubule, a segment that also expresses tissue kallikrein (KLK-1), raises two questions. Are the genes expressed in the same or in different cells of connecting tubule? Does this topography support the hypothesis that KLK-1 activates prorenin or is it more likely that it affords coordinated gene regulation? METHODS: Renin and KLK-1 were examined by immunostaining and in situ hybridization. Renin activation by KLK-1 was investigated in vitro. In vivo, excretion of prorenin and active renin was compared in mice homozygous for targeted inactivation of KLK-1 (TK(-/-)) and normal littermates (TK(+/+)). RESULTS: Using in situ immunostaining for renin and in situ hybridization for KLK-1 mRNA, we found that connecting tubule cells expressing renin also expressed KLK-1. We confirmed in vitro activation of prorenin by KLK-1, but found no difference in the ratio of active renin to prorenin in urine of TK(-/-) and TK(+/+) animals. Compared to TK(+/+) controls, TK(-/-) mice exhibited significantly lower 24-hour excretion of prorenin (5.05 +/- 1.16 mg Ang I/hour vs. 9.39 +/- 1.96 mg Ang I/hour, P < 0.05) and active renin (1.98 +/- 0.25 mg Ang I/hour vs. 3.58 +/- 0.39 mg Ang I/hour, P < 0.05), with no difference in either urine volumes or plasma renin concentrations. CONCLUSION: Direct interaction between renin and KLK-1, not ruled out in vitro, is not supported in vivo. By contrast, lower excretion of active renin and prorenin in TK(-/-) compared to TK(+/+) suggest coordinated regulation of the two proteins in their participation to collecting duct function.

Animals↗

PubMed2003

Bone mineral measurements in mice: comparison of two devices.

Animal models are widely used to explore the pathogenesis and management of osteoporosis. Mice are increasingly being used in animal models. We have evaluated the precision, accuracy, and ability to monitor changes in bone mineral measurements of mice with the Piximus and Hologic QDR 2000 devices. One hundred and twenty-two C57/BL6 mice were used in this study; 70 of them were put on a low calcium diet and followed prospectively for 14 wk. They were measured using both devices at baseline and at wk 14. Using the Piximus, we measured the whole body, the tibia, and two caudal vertebrae. Using the Hologic, we measured the tibia, which we divided into three equal parts. The remaining mice were used to evaluate the precision and accuracy of the measurement. The accuracy, which was determined only for the Hologic device, revealed a mean difference between the in vivo bone mineral content (BMC) and the ash weight of 0.1 mg. The precision, evaluated from the coefficient of variation (%) and the Smallest Detectable Difference (SDD, in absolute values) was good for both devices, confirming their ability to detect small differences in longitudinal studies: as little as 0.004 g for the BMC of the total tibia on both devices, and 0.003 g/cm2 for whole body bone mineral density (BMD) on the Piximus. The BMC found using the two devices was comparable, whereas the BMD obtained on the Hologic device was nearly double that found using the Piximus. The comparison of the results by Bland and Altman's method showed that the difference between the results was not dependent on the magnitude of the measurement. We concluded that bone density and bone-density changes in mice can be measured precisely in vivo using the Hologic and Piximus devices; the latter being able to measure the whole body BMD with good precision.

Absorptiometry, Photon↗

PubMed2002

Altered renin synthesis and secretion in the kidneys of heterozygous mice with a null mutation in the TGF-beta(2) gene.

Transforming growth factors beta (TGF-betas) are peptides involved in autocrine and paracrine control of cell growth and differentiation. In the kidneys, TGF-beta(2) has been shown to localize specifically in renin-producing cells in various conditions stimulating the renin response. To test in vivo the functional role of TGF-beta(2), the renin response was investigated in mice heterozygous for a null mutation of the TGF-beta(2) gene, which had a twofold reduction in the amount of TGF-beta(2) mRNA. Although the increase in plasma renin concentration triggered by dehydration was not different from wild-type mice, renal renin mRNA and protein levels were higher in mutant mice under hydrated or dehydrated conditions. These data suggest that TGF-beta(2) exerts an inhibitory effect on renin synthesis and release from the juxtaglomerular apparatuses.

Animals↗

PubMed2002

Cardiovascular phenotypes of kinin B2 receptor- and tissue kallikrein-deficient mice.

To clarify the role of the kallikrein-kinin system in cardiovascular homeostasis, the systemic and regional hemodynamics of kinin B2 receptor-deficient (B2-/-) and tissue kallikrein-deficient (TK-/-) mice were compared with their wild-type (WT) littermates on a pure C57BL/6 genetic background. B2-/-, TK-/-, and WT adult mice were normotensive and displayed normal hemodynamic (left ventricular [LV] pressure, cardiac output, total peripheral resistance, dP/dt(max)) and echocardiographic (septum and LV posterior wall thickness, LV diameter, LV mass, and LV fractional shortening) parameters. However, heart rate was lower in B2-/- mice compared with TK-/- and WT mice. In addition, B2-/- mice, but not TK-/- mice, exhibited lower coronary and renal blood flows and greater corresponding vascular resistances than did WT mice, indicating a tonic physiological vasodilating effect of bradykinin in these vascular beds. However, maximal coronary vasodilatation capacity, estimated after dipyridamole infusion, was similar in the 3 groups of mice. B2-/- mice were significantly more sensitive than were TK-/- mice to the vasoconstrictor effects of angiotensin II and norepinephrine. Finally, renin mRNA levels were significantly greater in B2-/- mice and smaller in TK-/- mice compared with WT mice. Taken together, these results indicate that under basal conditions, the kinin B2 receptor is not an important determinant of blood pressure in mice but is involved in the control of regional vascular tone in the coronaries and the kidneys. The phenotypic differences observed between TK-/- and B2-/- mice could be underlain by tissue kallikrein kinin-independent effect and/or kinin B1 receptor activation.

Angiotensin II↗

PubMedDate not supplied

Structure and expression of two kininogen genes in mice.

Kininogens serve dual functions by forming a scaffold for the assembly of the protein complex initiating the surface-activated blood coagulation cascade and as precursors for the kinin hormones. While rats have three kininogen genes, for mice, cattle, and humans only one gene has been described. Here, we present sequence and expression data of a second mouse kininogen gene. The two genes, kininogen-I and kininogen-II, are located in close proximity on chromosome 16 in a head-to-head arrangement. In liver and kidney, both genes are expressed and for each gene three alternative splice variants are synthesized. Two of them are the expected high and low molecular weight isoforms known from all mammalian kininogens. However, for both genes also a third, hitherto unknown splice variant was detected which lacks part of the high molecular weight mRNA due to splicing from the low molecular weight donor site to alternative splice acceptor sites in exon 10. The physiological functions of the six kininogen isoforms predicted by these findings need to be determined.

Alternative Splicing↗