Masum Md Abdul, Ichii Osamu, Elewa Yaser Hosny Ali, Kon Yasuhiro
Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Department of Anatomy, Histology and Physiology, Faculty of Animal Science and Veterinary Medicine, Sher-e-Bangla Agricultural University, Dhaka, Bangladesh.
Front Immunol. 2021 Jan 22;11:606488. doi: 10.3389/fimmu.2020.606488. eCollection 2020.
While chronic kidney disease is prevalent in adults, obstructive nephropathy (ON) has been reported in both young and old patients. In ON, tubulointerstitial lesions (TILs) have been widely investigated, but glomerular lesions (GLs) have been largely neglected. Here, we show a novel mechanism underlying GL development in ON in young and old mice. TILs develop earlier than GLs owing to infiltration of inflammatory cells in the tubulointerstitium, but GLs develop following the activation of () even though the absence of inflammatory cells infiltrating the glomerulus. TLR8 and interleukin 1 beta (IL1β) proteins colocalize with reducing podocyte function markers (PFMs), indicating the activation of TLR8 signaling in injured podocytes. Furthermore, glomerular and serum levels of miR-21, an endogenous ligand for , were higher in the ON mouse model than in the sham control. The glomerular expression of positively correlates with miR-21 and the downstream cytokines and and negatively correlated with PFMs ( and ). We also show the colocalization of TLR8 and IL1β proteins with reducing PFMs in both obstructed and collateral kidney of young and old mice. Furthermore, study results revealed higher expression of and its downstream cytokines in glomeruli from obstructed kidneys following treatment with miR-21 mimic than in the control. In conclusion, the overexpression of may serve as a plausible mechanism underlying GL development in ON through podocyte injury.
虽然慢性肾脏病在成年人中很普遍，但阻塞性肾病（ON）在年轻和老年患者中均有报道。在ON中，肾小管间质病变（TILs）已得到广泛研究，但肾小球病变（GLs）在很大程度上被忽视了。在此，我们展示了年轻和老年小鼠ON中GL发展的一种新机制。由于肾小管间质中炎性细胞的浸润，TILs比GLs更早出现，但即使没有炎性细胞浸润肾小球，GLs在（）激活后仍会发展。Toll样受体8（TLR8）和白细胞介素1β（IL1β）蛋白与减少的足细胞功能标志物（PFMs）共定位，表明受损足细胞中TLR8信号通路被激活。此外，ON小鼠模型中miR - 21（一种（）的内源性配体）的肾小球和血清水平高于假手术对照组。（）的肾小球表达与miR - 21及其下游细胞因子（）和（）呈正相关，与PFMs（）和（）呈负相关。我们还展示了年轻和老年小鼠阻塞性肾脏和侧支肾脏中TLR8和IL1β蛋白与减少的PFMs的共定位。此外，研究结果显示，用miR - 21模拟物处理后，阻塞性肾脏肾小球中（）及其下游细胞因子的表达高于对照组。总之，（）的过表达可能是通过足细胞损伤导致ON中GL发展的一种合理机制。
