Myeloid-specific targeting of Notch ameliorates murine renal fibrosis via reduced infiltration and activation of bone marrow-derived macrophage

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2 macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.

Application of Brain -computer Interface Technology in Medical Field / 医学信息学杂志

The paper introduces the structure and working principle of brain -computer interface system, elaborates the application of the technology in medical field, including automatic detection and classification of epilepsy, rehabilitation training and anesthetic depth monitoring, pointing out the challenges brain -computer interface technology faces.

Effect of macrophage polarization on interstitial fibrosis in mouse unilateral ureteral obstruction model / 中华肾脏病杂志

Objective To investigate the effect of macrophage polarization on tubulointerstitial fibrosis of mouse unilateral ureteral obstruction(UUO) model.Methods Twelve male C57BL/6J mice were employed,each of which with an age of 8 to 10 weeks.UUO model was established with these mice with the method of unilateral ureteral ligation.Mice were then sacrificed on the 7th and 14th day respectively after operation,and renal tissue specimens were obtained.The authors detected collagen deposition by Masson staining,and alpha smooth muscle actin (alpha SMA) as well as collagen type Ⅰ (Coll-1) mRNA by real-time quantitative PCR.The authors also detected the degree of renal interstitial macrophages infiltration and expression changes of polarization by immunofluorescence staining.Results Compared with the mice that were observed on the 7th day after operation,the degree of renal interstitial fibrosis in mice observed on the 14th day after operation was comparatively serious,the difference shown by semi-quantitative results was statistically significant (P ＜ 0.05).Moreover,mice observed on the 14th day after operation have more M2 macrophages,the difference between two groups of mice was statistically significant (P ＜ 0.05).On the contrary,there was no statistically significant difference in the degree of M1 macrophages infiltration between these two groups of mice.Conclusions In the renal interstitial fibrosis model induced by UUO,the degree of macrophage infiltration increased significantly,mainly resulted from M2 macrophage infiltration,suggesting that M2 macrophages were involved in the formation of renal fibrosis.