The Effect Of Nicotine In Promoting Renal Interstitial Fibrosis Through The Upregulation Of α7 NAChR

Objective:Chronic kidney disease(CKD)is a global public health problem,with a prevalence rate of more than 10% in adults in China.Renal fibrosis is the common pathway leading to endstage renal disease(ESRD)after many kinds of renal injury.At present,there is a lack of effective measures to delay and treat it.Epidemiological studies have shown that smoking can accelerate the progression of chronic kidney disease caused by various causes.Our previous study found that nicotine mediates X-linked inhibitor of apoptosis protein(XIAP)to promote renal tubular epithelial interstitial transformation.In recent years,it has been found that nicotine participates in the progression of CKD through α 7 nicotine acetylcholine receptor(α7 nAChR).The purpose of this study is to clarify the effect of nicotine in the progression of renal interstitial fibrosis mediated by α7 nAChR in vivo and clinicopathology.Methods:We established a CKD mouse model by unilateral ureteral obstruction(UUO),and collected renal biopsy specimens from patients with CKD for clinical verification.In the animal experiment,UUO mice were intraperitoneally injected with nicotine and interfered with α7 nAChR antagonist.Immunohistochemical staining,hematoxylin-eosin(HE)staining and Masson staining were used to detect the expression of α7 nAChR,XIAP and renal fibrosis markers.Then the expression of α7 nAChR and XIAP in renal tissue of patients with CKD was detected by paraffin section immunohistochemical staining.In the CKD smoking group,the correlation between the expression of them and the degree of renal fibrosis was analyzed.Results:In CKD mouse model,nicotine can significantly up-regulate the expression of α7nAChR,XIAP and fibrosis index Vimentin,aggravate renal tubular injury,promote interstitial collagen deposition,and then promote the occurrence and development of renal interstitial fibrosis.However,these effects were inhibited by α7 nAChR antagonist MLA.Through a retrospective study,we compared the smoking group with non-smoking group in patients with CKD.The results showed that the expression of α7 nAChR and XIAP in the kidney of CKD smoking group was significantly higher than that of CKD non-smoking group.The results of correlation analysis showed that in CKD smoking group,the expression of α7 nAChR and XIAP was positively correlated with the degree of renal interstitial fibrosis.Conclusion:In the mouse model of unilateral ureteral ligation,nicotine promotes the progression of renal fibrosis through the upregulation the of α7 nAChR-mediated XIAP,so targeting inhibition of α7 nAChR expression can further clarify the mechanism of nicotine in promoting the progression of chronic kidney disease.