Serum Iron Overload Activates the SMAD Pathway and Hepcidin Expression of Hepatocytes via SMURF1

作     者：Ning Zhang Pengyao Yang Yanmeng Li Qin Ouyang Fei Hou Guixin Zhu Bei Zhang Jian Huang Jidong Jia Anjian Xu 

作者机构：Experimental and Translational Research CenterBeijing Friendship HospitalCapital Medical UniversityBeijingChina Department of GastroenterologyBeijing Shunyi HospitalBeijingChina Department of Critical Liver DiseasesBeijing Friendship HospitalCapital Medical UniversityBeijingChina MOE Key Laboratory of Protein ScienceSchool of Life SciencesTsinghua UniversityBeijingChina Liver Research CenterBeijing Friendship HospitalCapital Medical UniversityBeijingChina 

出 版 物：《Journal of Clinical and Translational Hepatology》 (临床与转化肝病杂志（英文版）)

年 卷 期：2024年第12卷第3期

页      面：227-235页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.82370898) Beijing Natural Science Foundation(No.7202034) 

主　　题：BMP/SMAD pathway Hepcidin Holo-transferrin Ubiquitin-proteasome degradation Hemochromatosis 

摘      要：Background and Aims:Liver iron overload can induce hepatic expression of bone morphogenic protein(BMP)6 and activate the BMP/SMAD ***,serum iron overload can also activate SMAD but does not induce BMP6 ***,the mechanisms through which serum iron overload activates the BMP/SMAD pathway remain *** study aimed to clarify the role of SMURF1 in serum iron overload and the BMP/SMAD ***:A cell model of serum iron overload was established by treating hepatocytes with 2 mg/mL of holo-transferrin(Holo-Tf).A serum iron overload mouse model and a liver iron overload mouse model were established by intraperitoneally injecting 10 mg of Holo-Tf into C57BL/6 mice and administering a high-iron diet for 1 week followed by a low-iron diet for 2 *** blotting and real-time PCR were performed to evaluate the activation of the BMP/SMAD pathway and the expression of ***:Holo-Tf augmented the sensitivity and responsiveness of hepatocytes to *** E3 ubiquitin-protein ligase SMURF1 mediated Holo-Tf-induced SMAD1/5 activation and hepcidin expression;specifically,SMURF1 expression dramatically decreased when the serum iron concentration was ***,the expression of SMURF1 substrates,which are important molecules involved in the transduction of BMP/SMAD signaling,was significantly ***,in vivo analyses confirmed that SMURF1 specifically regulated the BMP/SMAD pathway during serum iron ***:SMURF1 can specifically regulate the BMP/SMAD pathway by augmenting the responsiveness of hepatocytes to BMPs during serum iron overload.