The aim of the present study was to investigate whether pharmacological enhancement of the renal kallikrein-kinin system using the vasopeptidase inhibitor omapatrilat plays a direct role in modulating the fibrotic responses of human mesangial cells to injury. Treatment with 40 micromol/L omapatrilat was able to reduce macrophage-conditioned medium (MPCM)-induced fibronectin levels without affecting mRNA expression. MPCM injury also suppressed kallikrein and low molecular weight kininogen mRNA. Omapatrilat was able to attenuate this suppression. Bradykinin levels in contrast were increased by MPCM and treatment with omapatrilat further augmented levels. Co-incubation with the bradykinin B2 receptor antagonist HOE 140 attenuated the omapatrilat-induced lowering of fibronectin. Moreover, inhibition of cGMP release had a similar effect. Paradoxically, RT-PCR and Southern blotting demonstrated that bradykinin B2 receptor mRNA levels were down regulated in response to omapatrilat. Western blotting supported this data. Supernatant levels of tissue plasminogen activator (tPA), a product of bradykinin stimulation, were decreased by omapatrilat while cell associated tPA levels were increased. Matrix metalloproteinase-9 (MMP-9) mRNA expression was up regulated by omapatrilat treatment, although no difference in active zymogen levels was observed. In conclusion enhancement of kallikrein-kinin system appears to play a direct role in promoting anti-fibrotic responses in MPCM-injured human mesangial cells.
-CRT improves DHF-induced alterations of Na(+) channel function, especially suppression of INa-L, thus abbreviating the APD and reducing the frequency of EADs. Changes in the levels of phosphorylated CaMKII suggest a molecular pathway for regulation of INa by biventricular pacing of the failing hear...
Observe in three-dimensional (3D) systems. Thermal fluctuations in 2D systems
Are enhanced, and they prevent the conventional Bose-Einstein condensation
(BEC) at non-zero temperatures by destroying the long-range order. However, a
Phase transition to a superfluid phase is still expected to occur...
We investigate both analytically and numerically violations of a Leggett-Garg
Inequality (LGI) for a composite quantum system in contact with two separate
Reservoirs at different temperatures. Remarkably we find that LGI violations
Can be enhanced when a heat current is established at low temperatur...
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