Reliable Surface Area Assessment of Wet and Dry Nonporous and Nanoporous Particles: Nuclear Magnetic Resonance Relaxometry and Gas Physisorption.

The reliable assessment of surface area is extremely important for many applications, e.g., catalysis, separation, and energy storage/conversion. Within this context, major progress has been made concerning the textural characterization of porous materials in the gas/dry state, e.g., gas physisorption and mercury porosimetry. However, these methods are not sufficient for the characterization of wet materials utilized in liquid-phase processes. For this, the application of nuclear magnetic resonance (NMR) relaxometry has been considered, but a systematic and rigorous assessment of the applicability of NMR relaxometry for reliable surface and pore size characterization of nanoporous materials is missing. Hence, we present a systematic study in which we assess the applicability of NMR relaxometry for reliable surface area assessment utilizing for the first time true surface area benchmark data based on argon 87 K adsorption on nonporous particles (silica and carbon black) coupled with the development of an advanced methodology including the investigation of the choice of the probe molecule and the effect of its accessibility to the pore network. Our results show that the method provides a fast (a few minutes per measurement) and reliable surface area of silica and carbon black model materials immersed in a liquid phase. In addition, our work clearly demonstrates the potential of NMR relaxometry for the targeted surface area assessment of defined pore classes (here ultramicropores) and suggests a new methodology for the characterization of pore entrances (pore window size). Furthermore, we investigate the effect of wettability and suggest that NMR relaxometry could be developed into a unique tool for assessing the wetting characteristics of adsorbate phases on pore surfaces. This fundamental study can be considered a first major step in enabling NMR relaxometry for reliable surface area assessment for wet materials, particularly relevant for materials used in processes occurring in a liquid phase.

P2Y2R Signaling Is Involved in the Onset of Glomerulonephritis.

Endogenously released adenosine-5'-triphosphate (ATP) is a key regulator of physiological function and inflammatory responses in the kidney. Genetic or pharmacological inhibition of purinergic receptors has been linked to attenuation of inflammatory disorders and hence constitutes promising new avenues for halting and reverting inflammatory renal diseases. However, the involvement of purinergic receptors in glomerulonephritis (GN) has only been incompletely mapped. Here, we demonstrate that induction of GN in an experimental antibody-mediated GN model results in a significant increase of urinary ATP-levels and an upregulation of P2Y2R expression in resident kidney cells as well as infiltrating leukocytes pointing toward a possible role of the ATP/P2Y2R-axis in glomerular disease initiation. In agreement, decreasing extracellular ATP-levels or inhibition of P2R during induction of antibody-mediated GN leads to a reduction in all cardinal features of GN such as proteinuria, glomerulosclerosis, and renal failure. The specific involvement of P2Y2R could be further substantiated by demonstrating the protective effect of the lack of P2Y2R in antibody-mediated GN. To systematically differentiate between the function of P2Y2R on resident renal cells versus infiltrating leukocytes, we performed bone marrow-chimera experiments revealing that P2Y2R on hematopoietic cells is the main driver of the ATP/P2Y2R-mediated disease progression in antibody-mediated GN. Thus, these data unravel an important pro-inflammatory role for P2Y2R in the pathogenesis of GN.

mTORC2 critically regulates renal potassium handling.

The mTOR pathway orchestrates cellular homeostasis. The rapamycin-sensitive mTOR complex (mTORC1) in the kidney has been widely studied; however, mTORC2 function in renal tubules is poorly characterized. Here, we generated mice lacking mTORC2 in the distal tubule (Rictorfl/fl Ksp-Cre mice), which were viable and had no obvious phenotype, except for a 2.5-fold increase in plasma aldosterone. Challenged with a low-Na+ diet, these mice adequately reduced Na+ excretion; however, Rictorfl/fl Ksp-Cre mice rapidly developed hyperkalemia on a high-K+ diet, despite a 10-fold increase in serum aldosterone levels, implying that mTORC2 regulates kaliuresis. Phosphorylation of serum- and glucocorticoid-inducible kinase 1 (SGK1) and PKC-α was absent in Rictorfl/fl Ksp-Cre mice, indicating a functional block in K+ secretion activation via ROMK channels. Indeed, patch-clamp experiments on split-open tubular segments from the transition zone of the late connecting tubule and early cortical collecting duct demonstrated that Ba2+-sensitive apical K+ currents were barely detectable in the majority of Rictorfl/fl Ksp-Cre mice. Conversely, epithelial sodium channel (ENaC) activity was largely preserved, suggesting that the reduced ability to maintain K+ homeostasis is the result of impaired apical K+ conductance and not a reduced electrical driving force for K+ secretion. Thus, these data unravel a vital and nonredundant role of mTORC2 for distal tubular K+ handling.

mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress.

Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell metabolism and autophagy. Despite widespread clinical use of mTORC1 inhibitors, the role of mTORC1 in renal tubular function and kidney homeostasis remains elusive. By using constitutive and inducible deletion of conditional Raptor alleles in renal tubular epithelial cells, we discovered that mTORC1 deficiency caused a marked concentrating defect, loss of tubular cells, and slowly progressive renal fibrosis. Transcriptional profiling revealed that mTORC1 maintains renal tubular homeostasis by controlling mitochondrial metabolism and biogenesis as well as transcellular transport processes involved in countercurrent multiplication and urine concentration. Although mTORC2 partially compensated for the loss of mTORC1, exposure to ischemia and reperfusion injury exaggerated the tubular damage in mTORC1-deficient mice and caused pronounced apoptosis, diminished proliferation rates, and delayed recovery. These findings identify mTORC1 as an important regulator of tubular energy metabolism and as a crucial component of ischemic stress responses.