Study on the role and molecular mechanism of HMGN1 in acute kidney injury based on the NLRP3 inflammatory pathway
LUO Yuhan
SHAO Xingqin
ZHANG Lang
XIE Ying
YUAN Jing
ZHA Yan
LIN Xin
Abstract：Objective To study the regulatory role of NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome in acute kidney injury(AKI)mediated by high-mobility group nucleosome-binding protein 1(HMGN1)and its downstream Toll-like receptor 4(TLR4)-nuclear factor-kappa B(NF-κB)signaling pathways.Methods Eighteen C57BL/6 mice were selected and randomly divided into control group,AKI group and cytokine release inhibitory drug 3(CRID3)group(AKI+NLRP inhibitor),with 6 mice in each group.A mouse model of AKI induced by ischemia-reperfusion(I/R)was established by using the bilateral renal pedicle clamping method.The changes in renal function were evaluated by detecting the levels of serum blood urea nitrogen(BUN),serum creatinine(Scr)and cystatin C.The pathological changes in renal tissues were observed by using hematoxylin-eosin(HE)staining,Masson staining and Sirius Red staining.The expressions of HMGN1,NLRP3 and TLR4 in the renal tissues were detected by using immunohistochemical staining and Western blot method.The levels of inflammatory factors of interleukin-1(IL-1),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum were detected by using enzyme-linked immunosorbent assay(ELISA).Results Compared with those in the control group,the levels of serum BUN,Scr and cystatin C were significantly increased(P＜0.05),and the pathological injuries of the renal tissues were aggravated,with renal tubular necrosis,interstitial fibrosis and inflammatory cell infiltration,and the expressions of HMGN1,NLRP3 and TLR4 proteins in the renal tissues were significantly increased(P＜0.05),and the levels of serum IL-1,IL-6 and TNF-α were significantly increased in the AKI group(P＜0.05).Compared with those in the AKI group,the levels of serum BUN,Scr and cystatin C were significantly decreased(P＜0.05),and the pathological injuries,inflammation and fibrosis of the renal tissues were alleviated,and the expressions of HMGN1,NLRP3 and TLR4 proteins in the renal tissues were significantly decreased(P＜0.05),and the levels of serum IL-1,IL-6 and TNF-α were significantly decreased in the CRID3 group(P＜0.05).Conclusion NLRP3 participates in the pathological process of AKI by regulating the expression of HMGN1 and the downstream TLR4 signaling pathway.Inhibiting the expression of NLRP3 can improve renal function,alleviate pathological injuries and inflammatory response in renal tissues.
Keywords：Acute kidney injury(AKI)High-mobility group nucleosome-binding protein 1(HMGN1)InflammationCytokinesInflammasome
Publication Date：2025-12-30
Online Publishing Date：2026-01-16(First online date of this platform, not the publication date of the document)
Pages：6( 1360-1365 )