STAT1 regulates interferon-γ-induced angiotensinogen and MCP-1 expression in a bidirectional manner in primary cultured mesangial cells

Objective: Intrarenal interferon-γ significantly contributes to the development of glomerular injury in which angiotensinogen and monocyte chemoattractant protein 1 levels are elevated. However, the exact nature of the role that interferon-γ plays in regulating angiotensinogen and monocyte chemoattractant protein 1 expression has not been fully delineated. Therefore, the aim of this study was to investigate the role that interferon-γ plays in angiotensinogen and monocyte chemoattractant protein 1 expression. Methods: Primary cultured rat mesangial cells were treated with 0–20 ng/mL interferon-γ for 2, 8 or 24 hours. Expression levels of angiotensinogen, monocyte chemoattractant protein 1, suppressors of cytokine signaling 1, an intracellular suppressor of Janus kinase-signal transducers and activators of transcription signaling and activity of the Janus kinase-signal transducers and activators of transcription pathway were evaluated by reverse transcriptase polymerase chain reaction and western blot analysis. Results: Interferon-γ increased angiotensinogen expression in mesangial cells with maximal augmentation observed following 5 ng/mL interferon-γ at 8 hours of treatment (1.87 ± 0.05, mRNA, relative ratio). Further increases were reduced or absent using higher concentrations of interferon-γ. Following treatments, monocyte chemoattractant protein 1 expression was induced in a linear dose-dependent manner (6.85 ± 0.62-fold by 20 ng/mL interferon-γ at 24 hours). In addition, interferon-γ induced STAT1 phosphorylation and suppressors of cytokine signaling 1 expression in a linear dose-dependent manner. The suppression of STAT1 and suppressors of cytokine signaling 1 expression by small interference RNAs facilitated an increase in interferon-γ-induced angiotensinogen expression, indicating that these two factors negatively regulate angiotensinogen expression. In contrast, the increase in interferon-γ-induced monocyte chemoattractant protein 1 expression was attenuated in STAT1-deficient mesangial cells, suggesting that STAT1 positively regulates monocyte chemoattractant protein 1 expression in mesangial cells. Conclusion: These results demonstrate that while interferon-γ increases both angiotensinogen and monocyte chemoattractant protein 1 expression, STAT1 plays an opposing role in the regulation of each factor in mesangial cells

New Analytical Methods for the Surface/ Interface and the Micro-Structures in Advanced Nanocomposite Materials by Synchrotron Radiation

Analytical methods of surface/interface structure and micro-structure in advanced nanocomposite materials by using the synchrotron radiation are introduced. Recent results obtained by the energy-tunable and highly collimated brilliant X-rays, in-situ wide angle/small angle X-ray diffraction with high accuracy are reviewed. It is shown that small angle X-ray scattering is one of the best methods to characterize nanoparticle dispersibility, filler aggregate/agglomerate structures and in-situ observation of hierarchical structure deformation in filled rubber under cyclic stretch. Grazing Incidence(small and wide angle) X-ray Scattering are powerful to analyze the sintering process of metal nanoparticle by in-situ observation as well as the orientation of polymer molecules and crystalline orientation at very thin surface layer (ca 7nm) of polymer film. While the interaction and conformation of adsorbed molecule at interface can be investigated by using high energy X-ray XPS with Enough deep position (ca 9 micron m).Received: 11 October 2010; Revised: 13 December 2010; Accepted: 23 December 201

Angiotensinogen expression in neonates

Background We recently demonstrated that preterm neonates have higher urinary angiotensinogen (AGT) levels than full-term neonates. Here, we tested the hypothesis that enhanced neonatal AGT expression is associated with intrarenal renin-angiotensin system (RAS) status during kidney development. Methods We prospectively recruited neonates born at our hospital and healthy children with minor glomerular abnormalities between April 2013 and March 2017. We measured neonatal plasma and urinary AGT levels at birth and one year later and assessed renal AGT expression in kidney tissues from neonates and healthy children using immunohistochemical (IHC) analysis. Results Fifty-four neonates and eight children were enrolled. Although there were no changes in plasma AGT levels, urinary AGT levels were significantly decreased one year after birth. Urinary AGT levels at birth were inversely correlated with gestational age, and urinary AGT levels at birth and one year later were inversely correlated with estimated glomerular filtration rate one year after birth. IHC analysis showed that renal AGT expression in neonates was higher than that in healthy children and inversely correlated with gestational age. Conclusions Enhanced AGT expression and urinary AGT excretion may reflect intrarenal RAS activation associated with kidney development in utero

Development of Coaxial Type flow microwave reactor

[EN] We have developed a flow microwave reactor with a coaxial cavity. It comprises a cylindrical cavity of 100 mm inside diameter, a metal rod along its center axis, and a spiral glass tube for flowing solvents and reactants, as shown in Fig.1. When the input port of microwave is placed at the end of the metal rod, the TEM mode is excited in the cylindrical chamber due to the presence of the metal rod. Simulations of the electric field and the magnetic field within the coaxial cavity are shown in Fig.2. This configuration was confirmed suitable for rapid and continuous microwave syntheses of various functional metal complexes. Experimental results are presented of Ir(Ⅲ) complexes for OLED dopants and Ru(Ⅱ) complexes for various sensors. The application to rapid and continuous microwave synthesis of various functional metal complexes were performed in success. In the similar manner as the coaxial reaction chamber of 2.45GHz, a coaxial reaction chamber for 5.8GHz IMS band, dimension of 51mm in diameter and 50mm in height,　is designed The electric field distributions in the chamber and the temperature profiles of solvent are simulated using the commercial simulator (COMSOL Multiphysics) for 5.8 GHz, 5W microwave input. Using the simulation results appropriate dimensions of the chamber are determined for the 5.8 GHz operation. When water is used as a solvent the simulation shows that the temperature rises from20℃ to 95℃ after 300 seconds of the microwave irradiation.Matsumura, T.; Kishihara, M.; Urushihara, U. (2019). Development of Coaxial Type flow microwave reactor. En AMPERE 2019. 17th International Conference on Microwave and High Frequency Heating. Editorial Universitat Politècnica de València. 487-491. https://doi.org/10.4995/AMPERE2019.2019.9897OCS48749

Urinary ACE2 in pediatric IgA nephropathy

Background : Our previous studies demonstrated that the intrarenal renin-angiotensin system (RAS) status was activated in pediatric patients with chronic glomerulonephritis. In the present study, we tested the hypothesis that angiotensin-converting enzyme 2 (ACE2) expression in the kidney is associated with the development of pediatric IgA nephropathy. Methods : We analyzed urinary ACE2 levels and ACE2 expression in the kidney tissues of pediatric patients with IgA nephropathy treated with RAS blockade. Paired tests were used to analyze changes from the first to the second biopsy. Results : Urinary ACE2 levels were significantly decreased after RAS blockade treatment, accompanied by decreased ACE2 expression levels in kidney tissues, urinary protein levels and mesangial hypercellularity scores. Urinary ACE2 levels at the first biopsy were positively correlated with the ACE2 expression levels. Conclusions : These data suggest that urinary ACE2 is associated with ACE2 expression in the diseased kidney, which correlates with the pathogenesis of IgA nephropathy in pediatric patients

Transforming growth factor-β1 stimulates collagen matrix remodeling through increased adhesive and contractive potential by human renal fibroblasts

AbstractRenal tubulointerstitial fibrosis is the common final pathway leading to end-stage renal failure. Tubulointerstitial fibrosis is characterized by fibroblast proliferation and excessive matrix accumulation. Transforming growth factor-β1 (TGF-β1) has been implicated in the development of renal fibrosis accompanied by α-smooth muscle actin (α-SMA) expression in renal fibroblasts. To investigate the molecular and cellular mechanisms involved in tubulointerstitial fibrosis, we examined the effect of TGF-β1 on collagen type I (collagen) gel contraction, an in vitro model of scar collagen remodeling. TGF-β1 enhanced collagen gel contraction by human renal fibroblasts in a dose- and time-dependent manner. Function-blocking anti-α1 or anti-α2 integrin subunit antibodies significantly suppressed TGF-β1-stimulated collagen gel contraction. Scanning electron microscopy showed that TGF-β1 enhanced the formation of the collagen fibrils by cell attachment to collagen via α1β1 and α2β1 integrins. Flow cytometry and cell adhesion analyses revealed that the stimulation of renal fibroblasts with TGF-β1 enhanced cell adhesion to collagen via the increased expression of α1 and α2 integrin subunits within collagen gels. Fibroblast migration to collagen was not up-regulated by TGF-β1. Furthermore, TGF-β1 increased the expression of a putative contractile protein, α-SMA, by human renal fibroblasts in collagen gels. These results suggest that TGF-β1 stimulates fibroblast–collagen matrix remodeling by increasing both integrin-mediated cell attachment to collagen and α-SMA expression, thereby contributing to pathological tubulointerstitial collagen matrix reorganization in renal fibrosis

Angiotensin II Type 1 Receptor Blockers Reduce Urinary Angiotensinogen Excretion and the Levels of Urinary Markers of Oxidative Stress and Inflammation in Patients with Type 2 Diabetic Nephropathy

Objective To demonstrate that the administration of an angiotensin (Ang) II type 1 receptor (AT1R) blocker (ARB) inhibits the vicious cycle of high glucose (HG)-reactive oxygen species (ROS)-angiotensinogen (AGT)-Ang II-AT1R-ROS by suppressing ROSs and inflammation, thus ameliorating diabetic nephropathy (DN). Research Design and Methods Thirteen hypertensive DN patients were administered ARBs, and the following parameters were evaluated before and 16 weeks after the treatment: urinary AGT (UAGT), albumin (albumin-creatinine ratio: ACR), 8-hydroxydeoxyguanosine (8-OHdG), 8-epi-prostaglandin F2α (8-epi-PGF2α), monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and IL-10. Results ARB treatment reduced the blood pressure and urinary levels of AGT, ACR, 8-OHdG, 8-epi-PGF2α, MCP-1, and IL-6 but increased the urinary levels of IL-10. The reduction rate of UAGT correlated with the reduction rate of blood pressure; the reduction rates of the urinary ACR, 8-OHdG, 8-epi-PGF2α, MCP-1, and IL-6 levels; and the increase rate of the urinary IL-10 levels. Moreover, subjects who had high UAGT values at baseline exhibited higher reduction rates of urinary albumin excretion. Conclusions ARB-induced blockade of the abovementioned vicious cycle contributes to the renoprotective effects of ARBs in DN. The urinary levels of AGT could represent a predictive factor for reduced ACR in patients receiving ARB treatment