Renal tubule epithelia represent the primary site of damage in acute kidney injury (AKI), a process initiated and propagated by the infiltration of macrophages. Here we investigated the role of resident renal macrophages and dendritic cells in recovery from AKI after ischemia/reperfusion (I/R) injury or a novel diphtheria toxin-induced (DT-induced) model of selective proximal tubule injury in mice. DT-induced AKI was characterized by marked renal proximal tubular cell apoptosis. In both models, macrophage/dendritic cell depletion during the recovery phase increased functional and histologic injury and delayed regeneration. After I/R-induced AKI, there was an early increase in renal macrophages derived from circulating inflammatory (M1) monocytes, followed by accumulation of renal macrophages/dendritic cells with a wound-healing (M2) phenotype. In contrast, DT-induced AKI only generated an increase in M2 cells. In both models, increases in M2 cells resulted largely from in situ proliferation in the kidney. Genetic or pharmacologic inhibition of macrophage colony-stimulating factor (CSF-1) signaling blocked macrophage/dendritic cell proliferation, decreased M2 polarization, and inhibited recovery. These findings demonstrated that CSF-1-mediated expansion and polarization of resident renal macrophages/dendritic cells is an important mechanism mediating renal tubule epithelial regeneration after AKI.

No abstract

The mechanisms by which angiotensin II (Ang II) promotes renal fibrosis remain incompletely understood. Ang II both stimulates TGFb signaling and activates the EGF receptor (EGFR), but the relative contribution of these pathways to renal fibrogenesis is unknown. Using a murine model with EGFRdeficient proximal tubules, we demonstrate that upstream activation of EGFR-dependent ERK signaling is critical for mediating sustained TGFb expression in renal fibrosis. Persistent activation of the Ang II receptor stimulated ROS-dependent phosphorylation of Src, leading to sustained EGFRdependent signaling for TGFb expression. Either genetic or pharmacologic inhibition of EGFR significantly decreased TGFb-mediated fibrogenesis. We conclude that TGFb-mediated tissue fibrosis relies on a persistent feed-forward mechanism of EGFR/ERK activation through an unexpected signaling pathway, highlighting EGFR as a potential therapeutic target for modulating tissue fibrogenesis.

No abstract

Bee pollen has been praised for its good nutrition and therapeutic values. China is the largest producer in the world. Twelve common varieties of monofloral bee pollen collected from China's main producing regions were selected for nutritional composition analysis, including proximate contents, dietary fibers, amino acid distribution, fatty acid composition, and mineral elements. The proximate compositions mostly met the specifications regulating pollen load quality of China. Proline and glutamic acids were found to be the predominant amino acids in the form of both total amino and free amino acids. Lysine was the relative limiting amino acid. The percentage of total essential amino acids (TEAA) to total amino acids (TAA) reached the nutrition recommendation of the Food and Agricultural Organization (FAO). The major fatty acids, presented as mean values, were C18:3 (25.1%), C16:0 (19.6%), C18:1 (17.3%), C18:2 (8.78%), C22:0 (4.07%), and C18:0 (2.96%) acids. The proportions of C18:3 were generally higher than those of C18:2, and the ratio of total unsaturated fatty acids (TUS) to total saturated fatty acids (TS) was >1.0, except for Nelumbo nucifera Gaertn. pollen for the characteristic absence of C18:3 acids. High levels of beneficial elements such as K, Ca, Mg, Zn, Fe, Mn. and Cu were observed in pollen samples. The contents of detrimental trace elements of Cd, Pb, and Hg were primarily lower or not detected. However, more attention should be paid to a large amount of Al, with a concentration of >100 mg/kg DW in most samples. There were some significant differences between samples. On the whole, the Chinese bee pollen was evaluated as a good complement to diet.