Bread Crust Extract Promotes TEMT Process Via RAGE-NF-?B Pathway Triggers Inflammatory Responses

Advanced glycation end products are the general term for series of compounds which with a stable structure and produced by the Maillard reaction during the heat treatment process of foods.AGEs could lead to the state of intracellular oxidative stress and activate nuclear factor-?B(NF-?B)inflammatory signalling pathway via interacting with the receptor for advanced glycation end products(RAGE),mediated cell stress and inflammatory responses.Furthermore,AGEs also promote tubular epithelial-myofibroblast transdifferentitation(TEMT)in kidney tubular epithelial cells.However,present studies for AGEs focus on the activation of intracellular signaling pathways and downstream gene expression.Damages to cells or tissues of AGE-rich dietary are scarcely studied.In this study,bread crust extract(BCE)which rich in AGEs was performed as the object.And the human kidney tubular epithelial cells(HKCs)was cultured in vitro,then treated with different concentrations of BCE for 24 h.The activity inhibition of HKCs,the level of intracellular oxidative stress and the expression of RAGE mRNA were detected.The activation of intracellular NF-?B signaling pathway,the secretion of downstream inflammatory cytokines and TEMT process were also explored.The main conclusions of this study are as follows:(1)AGEs and CML are riched in bread crust and BCE,the levels of free AGEs were158.77AU/mg and 1319.00AU/mg in bread crust and BCE,respectively.The contents of free CML in bread crust and BCE were 1.9?g/g and 7.67?g/g.While the protein-bound CML conteints were up to 61.92?g/g and 11.54?g/g.Compared with bread crust,BCE contains more free AGEs or CML(P<0.01).(2)After BCE treated HKCs for 24 h,BCE were significantly inhibited the HKCs viability at 12 mg/mL(P<0.05).The contents of ROS,MDA and extracellular LDH secretion were significantly increased,while the activity of intracellular SOD was significangly decreased along with the increased concentration of BCE(0,4,8 and 12 mg/mL)(P<0.05).(3)BCE significantly increased the expression of RAGE mRNA and activated the NF-?B signaling pathway and promoted the nuclear inflammatory factors IL-1?,IL-6 and TNF-? expression.(4)BCE significantly increased the expression of ?-SMA mRNA and protein,whileinhibiting the expression of E-cadherin mRNA and protein,and then promote the TEMT process(P<0.01).The above conclusions can be drawn that BCE can destroied the balance of oxidative stress in HKCs and lead to the activation of NF-?B signaling pathway,increase the secretion of inflammatory cytokines like IL-1?,IL-6 and TNF-?,thus promoted the TEMT process,which resulted to the tubulointerstitial fibrosis.