期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS,2023年1867(1):194952 ISSN：1874-9399
作者机构：
[Wu, Zhibin; Huang, Yunyuan] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China;[Liu, Ke] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China. Electronic address: keliu2015@ccnu.edu.cn;[Min, Jinrong] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China. Electronic address: minjinrong@ccnu.edu.cn
摘要：
Ubiquitination is a fascinating post-translational modification that has received continuous attention since its discovery. In this review, we first provide a concise overview of the E3 ubiquitin ligases, delving into classification, characteristics and mechanisms of ubiquitination. We then specifically examine the ubiquitination pathways mediated by the N/C-degrons, discussing their unique features and substrate recognition mechanisms. Finally, we offer insights into the current state of development pertaining to inhibitors that target the N/C-degron pathways, as well as the promising advances in the field of PROTAC (PROteolysis TArgeting Chimeras). Overall, this review offers a comprehensive understanding of the rapidly-evolving field of ubiquitin biology.
期刊：
JOURNAL OF EXPERIMENTAL BOTANY,2023年74(6):1836-1852 ISSN：0022-0957
通讯作者：
Yang Li<&wdkj&>Xue-Bao Li
作者机构：
[Wang, Yao; Li, Yu; Zheng, Yong; Li, Xue-Bao; Zhang, Shi-Peng; Li, Yang; Cheng, Fan] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.
通讯机构：
[Yang Li; Xue-Bao Li] H;Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University , Wuhan 430079 , China
摘要：
Cotton fiber elongation is a critical growth phase that affects final fiber length. Morphological analysis indicated an asynchronous fiber elongation pattern between two cotton varieties, J7-1 and J14-1. Through phosphoproteomic analysis, a total of 89 differentially-phosphorylated proteins (DPPs) were identified in elongating fibers between J7-1 and J14-1. Gene ontology (GO) analysis showed that these DPPs were mainly enriched in sucrose synthase activity, transferase activity, and UDP-glycosyltransferase activity. In J14-1, the phosphorylation level of GhSUS2, a key sucrose synthase in the sucrose metabolism pathway, was significantly higher than that in J7-1. We further revealed that GhSUS2 positively regulates fiber elongation, and GhSUS2-silenced transgenic cotton displayed the phenotype of 'short fibers' compared with the controls. During fiber development, the residue Ser11 in the GhSUS2 protein is phosphorylated by the Ca2+-dependent protein kinases GhCPK84 and GhCPK93. Phosphorylated GhSUS2 is localized in the cytoplasm, whereas unphosphorylated GhSUS2 is localized in the plasma membrane. Moreover, abscisic acid (ABA) could promote the transcription and translation of GhCPK84 and GhCPK93, thereby enhancing the phosphorylation of GhSUS2 to impede fiber elongation. Thus, our data demonstrates that GhSUS2 plays a positive role in fiber development, but its phosphorylation by GhCPK84 and GhCPK93 hinders fiber elongation of cotton.
作者机构：
[Chen, Mingqing; Han, Qi; Wei, Zhaolan; Deng, Lingfu; Wang, Yunyi; Wang, Shuwei] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.;[Chen, Mingqing] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.
通讯机构：
[Chen, Mingqing] H;Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China. Electronic address:
摘要：
Previous studies suggest some link between formaldehyde exposure and harmful cardiovascular effects. But whether exposure to formaldehyde can cause blood pressure to rise, and if so, what the underlying mechanism is, remains unclear. In this study, C57BL/6 male mice were exposed to 0.1, 0.5, 2.5mg/m(3) of gaseous formaldehyde for 4hours daily over a three-week period. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) of the mice were measured by tail-cuff plethysmography, and any histopathological changes in the target organs of hypertension were investigated. The results showed that exposure to formaldehyde did cause a significant increase in blood pressure and heart rate, and resulted in varying degrees of damage to the heart, aortic vessels and kidneys. To explore the underlying mechanism, a specific inhibitor of angiotensin converting enzyme (ACE) was used to block the ACE/AT1R axis. We observed the levels of ACE and angiotensin II type 1 receptor (AT1R), as well as the bradykinin (BK) in cardiac cytoplasm. The data suggest that exposure to formaldehyde induced an increase in the expression of ACE and AT1R, and decreased the levels of BK. Strikingly, treatment with 5mg/kg/d ACE inhibitor can attenuate the increase in blood pressure and the pathological changes caused by formaldehyde exposure. This result has improved our understanding of whether, and how, formaldehyde exposure affects the development of hypertension.
通讯机构：
[Rong Peng] I;Institute of Entomology, School of Life Sciences, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, Central China Normal University, Wuhan 430079, China<&wdkj&>Author to whom correspondence should be addressed.
关键词：
fluorescent nanoparticle;RNA interference;sterol carrier protein-2;Helicoverpa armigera;growth and development;pest control
摘要：
Helicoverpa armigera is a polyphagous destructive lepidopteran pest with strong Bacillus thuringiensis (Bt) resistance. Cholesterol, a vital component for insect growth, can only be obtained from food, and its transfer and metabolism are regulated by sterol carrier protein-2 (SCP-2). This study examined whether H. armigera SCP-2 (HaSCP-2) gene expression, involved in cholesterol absorption, can be silenced by nanocarrier fluorescent nanoparticle-RNA interference (FNP-RNAi) by larval feeding and whether the silencing affected H. armigera development. Fluorescence microscopy showed that nanoparticle-siRNA was distributed in Ha cells and the larval midgut. FNP-HaSCP-2 siRNA suppressed HaSCP-2 expression by 52.5% in H.armigera Ha cells. FNP can effectively help deliver siRNA into cells, protect siRNA, and is not affected by serum. FNP-siRNA in vivo biological assays showed that HaSCP-2 transcript levels were inhibited by 70.19%, 68.16%, and 67.66% in 3rd, 4th, and 5th instar larvae, leading to a decrease in the cholesterol level in the larval and prepupal fatbodies. The pupation rate and adult emergence were reduced to 26.0% and 56.52%, respectively. This study demonstrated that FNP could deliver siRNA to cells and improve siRNA knockdown efficiency. HaSCP-2 knockdown by FNP-siRNA in vivo hindered H. armigera growth and development. FNP could enhance RNAi efficiency to achieve pest control by SCP-2-targeted FNP-RNAi.
关键词：
E. coli;E. coli arrays;IgA;IgG;alcoholic hepatitis;autoantibodies;human;immunology;inflammation
摘要：
The pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissues from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy. Employing human and Escherichia coli K12 proteome arrays, we profiled the antibodies extracted from explanted SAH, livers with other diseases, and HD livers. Compared with their counterparts extracted from livers with other diseases and HD, antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins and E. coli antigens. Further, both Ig- and E. coli-captured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion, and focal adhesion (IgG). Except IgM from primary biliary cholangitis livers, no common autoantigen was recognized by Ig- and E. coli-captured Ig from livers with other diseases. These findings demonstrate the presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in SAH livers.
作者机构：
[Sun, Keping; Li, Aoqiang; Li, Zhongle; Leng, Haixia; Feng, Jiang; Jin, Longru] Northeast Normal Univ, Jilin Prov Key Lab Anim Resource Conservat & Utili, Changchun, Peoples R China.;[Li, Aoqiang] Cent China Normal Univ, Sch Life Sci, Wuhan, Peoples R China.;[Li, Zhongle; Feng, Jiang] Jilin Agr Univ, Coll Life Sci, Changchun, Peoples R China.
通讯机构：
[Keping Sun; Jiang Feng] J;Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, China<&wdkj&>Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, China<&wdkj&>College of Life Science, Jilin Agricultural University, Changchun, China
摘要：
Skin acts as a mechanical barrier between the body and its surrounding environment and plays an important role in resistance to pathogens. However, we still know little regarding skin responses to physiological changes, particularly with regard to responses against potential pathogens. We herein executed RNA-seq on the wing of the Rhinolophus ferrumequinum to assess gene-expression variations at four physiological stages: pre-hibernation, hibernation (early-hibernation and late-hibernation), and post-hibernation, as well as the gene-expression patterns of infected and uninfected bats with the Pseudogymnoascus destructans (Pd). Our results showed that a greater number of differentially expressed genes between the more disparate physiological stages. Functional enrichment analysis showed that the down-regulated response pathways in hibernating bats included phosphorus metabolism and immune response, indicating metabolic suppression and decreased whole immune function. We also found up-regulated genes in post-hibernating bats that included C-type lectin receptor signalling, Toll-like receptor signalling pathway, and cell adhesion, suggesting that the immune response and skin integrity of the wing were improved after bats emerged from their hibernation and that this facilitated clearing Pd from the integument. Additionally, we found that the genes involved in cytokine or chemokine activity were up-regulated in late-hibernation compared to early-hibernation and that FOSB regulation of immune cell activation was differentially expressed in bats infected with Pd during late-hibernation, implying that the host's innate immune function was enhanced during late-hibernation so as to resist pathogenic infection. Our findings highlight the concept that maintenance of intrinsic immunity provides protection against pathogenic infections in highly resistant bats.
作者机构：
[Han, Fei; Dai, Xiongfeng; Wang, Yanling; Dai, XF; Zhu, Manlu; Wang, Qian; Mu, Haoyan] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan, Hubei, Peoples R China.
通讯机构：
[Dai, XF ] C;Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan, Hubei, Peoples R China.
摘要：
Growth and survival are key determinants of bacterial fitness. However, how resource allocation of bacteria could reconcile these two traits to maximize fitness remains poorly understood. Here, we find that the resource allocation strategy of Bacillus subtilis does not lead to growth maximization on various carbon sources. Survival-related pathways impose strong proteome constraints on B. subtilis. Knockout of a master regulator gene, spo0A, triggers a global resource reallocation from survival-related pathways to biosynthesis pathways, further strongly stimulating the growth of B. subtilis. However, the fitness of spo0A-null strain is severely compromised because of various disadvantageous phenotypes (e.g., abolished sporulation and enhanced cell lysis). In particular, it also exhibits a strong defect in peptide utilization, being unable to efficiently recycle nutrients from the lysed cell debris to maintain long-term viability. Our work uncovers a fitness trade-off between growth and survival that governed by Spo0A-mediated proteome allocation constraints in B. subtilis, further shedding light on the fundamental design principle of bacteria.
摘要：
INTRODUCTION: Aging is characterized by progressive metabolic dyshomeostasis that increases morbidity and mortality. Solutions for optimizing healthy aging are challenged by lacking appropriate biomarkers. Moreover, druggable targets to rejuvenate the aging-associated metabolic phenotypes remain unavailable. METHODS: Proteomics analysis was performed in a cohort of young and elderly adults. Circulating levels of insulin-like growth factor 1 (IGF-1) and fatty acid binding protein 4 (FABP4) were evaluated by ELISA. FABP4 was silenced in elderly mice by adeno-associated virus. Metabolic activities were measured by metabolic cages. Cognitive function was evaluated by Morris water maze. Glucose and lipid metabolism were evaluated by biochemistry assays with blood samples. RNA-seq in mouse liver was performed for transcriptome analysis. RESULTS: Among 9 aging-sensitive proteins shared by both male and female, FABP4 was identified as a reliable aging biomarker in both human and mouse. Silencing FABP4 in elderly mice significantly rejuvenated the aging-associated decline in metabolic activities. FABP4 knockdown reversed the aging-associated metabolic disorders by promoting degradation of cholesterol and fatty acids, while suppressing gluconeogenesis. Transcriptome analysis revealed a restoration of the pro-aging gene reprogramming towards inflammation and metabolic disorders in the liver after FABP4 knockdown. FABP4 overexpression promoted human LO2 cell senescence. Moreover, administration of an FABP4 inhibitor BMS309403 delivered metabolic benefits in elderly mice. CONCLUSION: Our findings demonstrate FABP4 as a reliable aging biomarker as well as a practicable target to improve healthy aging in the elderly.
作者机构：
[Zhou, Cheng; Liu, Ying; Yang, Shuaikang; Zang, Jianfeng; Liu, Xurui; Tian, Ye; Tang, Hanchuan] Huazhong Univ Sci & Technol, Sch Integrated Circuits, Wuhan 430074, Peoples R China.;[Zhou, Cheng; Liu, Ying; Kang, Tianyu; Yang, Shuaikang; Zang, Jianfeng; Liu, Xurui; Tian, Ye; Tang, Hanchuan] Huazhong Univ Sci & Technol, Wuhan Natl Lab Optoelect, Wuhan 430074, Peoples R China.;[Chen, Wei; Zhang, Shujie] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China.;[Chen, Qicai] Cent China Normal Univ, Sch Life Sci, Wuhan 430074, Peoples R China.;[Xiao, Hongjun] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Otorhinolaryngol, Wuhan 430022, Peoples R China.
通讯机构：
[Hongjun Xiao; Hongjun Xiao Hongjun Xiao Hongjun Xiao] D;[Wei Chen; Wei Chen Wei Chen Wei Chen] C;[Jianfeng Zang; Jianfeng Zang Jianfeng Zang Jianfeng Zang] S;College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 China<&wdkj&>School of Integrated Circuits and Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074 China<&wdkj&>The State Key Laboratory of Digital Manufacturing Equipment and Technology, Huazhong University of Science and Technology, Wuhan, 430074 China<&wdkj&>Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
摘要：
A bioinspired soft elastic metamaterial with a size equivalent to the current cochlear implant that can be seen as a prototype of passive artificial cochlea with a frequency resolution of 30 Hz is proposed. This work will inspire future work in the fabrication of totally implantable passive artificial cochlea that enables the users to hear naturally. Abstract Natural hearing which means hearing naturally like normal people is critical for patients with hearing loss to participate in life. Cochlear implants have enabled numerous severe hearing loss patients to hear voice functionally, while cochlear implant users can hardly distinguish different tones or appreciate music subject to the absence of rate coding and insufficient frequency channels. Here a bioinspired soft elastic metamaterial that reproduces the shape and key functions of the human cochlea is reported. Inspired by human cochlea, the metamaterials are designed to possess graded microstructures with high effective refractive index distributed on a spiral shape to implement position‐related frequency demultiplexing, passive sound enhancements of 10 times, and high‐speed parallel processing of 168‐channel sound/piezoelectric signals. Besides, it is demonstrated that natural hearing artificial cochlea has fine frequency resolution up to 30 Hz, a wide audible range from 150–12 000 Hz, and a considerable output voltage that can activate the auditory pathway in mice. This work blazes a promising trail for reconstruction of natural hearing in patients with severe hearing loss.
摘要：
The Drosophila testis is an excellent system for studying the process from germ stem cells to motile sperm, including the proliferation of male germ cells, meiosis of primary spermatocytes, mitochondrial morphogenesis, and spermatid individualization. We previously demonstrated that ocnus (ocn) plays an essential role in male germ cell development. Among those genes and proteins whose expression levels were changed as a result of ocn knockdown, cytochrome c1-like (cyt-c1L) was downregulated significantly. Here, we show that cyt-c1L is highly expressed in the testis of D. melanogaster. Knockdown or mutation of cyt-c1L in early germ cells of flies resulted in male sterility. Immunofluorescence staining showed that cyt-c1L knockdown testes had no defects in early spermatogenesis; however, in late stages, in contrast to many individualization complexes (ICs) composed of F-actin cones that appeared at different positions in control testes, no actin cones or ICs were observed in cyt-c1L knockdown testes. Furthermore, no mature sperm were found in the seminal vesicle of cyt-c1L knockdown testes whereas the control seminal vesicle was full of mature sperm with needle-like nuclei. cyt-c1L knockdown also caused abnormal mitochondrial morphogenesis during spermatid elongation. Excessive apoptotic signals accumulated in the base of cyt-c1L knockdown fly testes. These results suggest that cyt-c1L may play an important role in spermatogenesis by affecting the mitochondrial morphogenesis and individualization of sperm in D. melanogaster.
作者：
Ke Liu;Jin Zhang;Yuqing Xiao;Ally Yang;Xiaosheng Song;...
期刊：
Journal of Biological Chemistry,2023年299(6):104734 ISSN：0021-9258
通讯作者：
Ke Liu<&wdkj&>Jinrong Min
作者机构：
[Ke Liu; Jin Zhang; Yuqing Xiao; Yunxia Chen] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, PR China;[Ally Yang; Timothy R. Hughes] Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada;[Xiaosheng Song; Yanjun Li] Structural Genomics Consortium and Department of Physiology, University of Toronto, Toronto, Ontario, Canada;[Jinrong Min] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, PR China<&wdkj&>Structural Genomics Consortium and Department of Physiology, University of Toronto, Toronto, Ontario, Canada
通讯机构：
[Ke Liu; Jinrong Min] H;Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, PR China<&wdkj&>Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, PR China<&wdkj&>Structural Genomics Consortium and Department of Physiology, University of Toronto, Toronto, Ontario, Canada
关键词：
BEN domain;BANP;BEND6;DNA methylation;X-ray crystallography
摘要：
The BEN domain-containing transcription factors regulate transcription by recruiting chromatin-modifying factors to specific chromatin regions via their DNA-binding BEN domains. The BEN domain of BANP has been shown to bind to a CGCG DNA sequence or an AAA-containing matrix attachment regions DNA sequence. Consistent with these in vivo observations, we identified an optimal DNA-binding sequence of AAATCTCG by protein binding microarray, which was also confirmed by our isothermal titration calorimetry and mutagenesis results. We then determined crystal structures of the BANP BEN domain in apo form and in complex with a CGCG-containing DNA, respectively, which revealed that the BANP BEN domain mainly used the electrostatic interactions to bind DNA with some base-specific interactions with the TC motifs. Our isothermal titration calorimetry results also showed that BANP bound to unmethylated and methylated DNAs with comparable binding affinities. Our complex structure of BANP-mCGCG revealed that the BANP BEN domain bound to the unmethylated and methylated DNAs in a similar mode and cytosine methylation did not get involved in binding, which is also consistent with our observations from the complex structures of the BEND6 BEN domain with the CGCG or CGmCG DNAs. Taken together, our results further elucidate the elements important for DNA recognition and transcriptional regulation by the BANP BEN domain-containing transcription factor.
作者机构：
[Wang, Wen-Shu; Gao, Xiang; Lu, Ying-Tang; Zhu, Jiang; Yan, Da-Wei; Li, Ting-Ting; Yuan, Ting-Ting; Hong, Li-Wei] Wuhan Univ, Renmin Hosp Wuhan Univ, Coll Life Sci, State Key Lab Hybrid Rice, Wuhan 430072, Peoples R China.;[Yang, Yun-Huang; Zhu, Jiang] Chinese Acad Sci, Innovat Acad Precis Measurement Sci & Technol, Natl Ctr Magnet Resonance Wuhan, State Key Lab Magnet Resonance & Atom Mol Phys, Wuhan 430071, Peoples R China.;[Ren, Feng] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Wang, Wen-Shu] Wuhan Acad Agr Sci, Inst Crop Sci, Wuhan 430345, Peoples R China.
通讯机构：
[Ying-Tang Lu; Ting-Ting Yuan] S;State Key Laboratory of Hybrid Rice, College of Life Sciences, Renmin Hospital of Wuhan University, Wuhan University , Wuhan 430072, China
摘要：
Jasmonic acid (JA) signaling plays a pivotal role in plant development and defense. MYC2 is a master transcription factor in JA signaling, and was found to be phosphorylated and negatively regulated by MAP kinase and receptor-like kinase. However, the kinases that positively regulate MYC2 through phosphorylation and promote MYC2-mediated activation of JA response have not been identified. Here, we identified CK2 as a kinase that phosphorylates MYC2 and thus regulates the JA signaling. CK2 holoenzyme can interact with MYC2 using its regulatory subunits and phosphorylate MYC2 at multiple sites with its catalytic subunits. Inhibition of CK2 activity in a dominant-negative plant line, CK2mut, repressed JA response. On the other hand, increasing CK2 activity by overexpression of CKB4, a regulatory subunit gene of CK2, enhanced JA response in a MYC2-dependent manner. Substitution of the Ser and Thr residues at phosphorylation sites of MYC2 by CK2 with Ala impaired MYC2 function in activating JA response. Further investigations evidenced that CK2 facilitated the JA-induced increase of MYC2 binding to the promoters of JA-responsive genes in vivo. Our study demonstrated that CK2 plays a positive role in JA signaling, and reveals a previously undiscovered mechanism that regulates MYC2 function.
期刊：
JOURNAL OF PROTEOME RESEARCH,2023年22(10):3254-3263 ISSN：1535-3893
通讯作者：
Li, YZ;Zhu, H
作者机构：
[Yan, Songxin; Li, YZ; Liu, Chenxi; Li, Liubing; Li, Yongzhe; Wen, Xiaoting] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Dept Clin Lab, Beijing 100730, Peoples R China.;[Liu, Chenxi] Sichuan Univ, West China Univ Hosp 2, Dept Clin Lab, Chengdu 610041, Peoples R China.;[Song, Guang] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.;[Song, Guang; Zhu, Heng; Zhu, H] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.;[He, Yangzhige] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Cent Res Lab, Beijing 100730, Peoples R China.
通讯机构：
[Li, YZ ] C;[Zhu, H ] J;Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Dept Clin Lab, Beijing 100730, Peoples R China.;Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
摘要：
Systemic sclerosis (SSc) is a systemic autoimmune disorder that leads to vasculopathy and tissue fibrosis. A lack of reliable biomarkers has been a challenge for clinical diagnosis of the disease. We employed a protein array-based approach to identify and validate SSc-specific autoantibodies. Phase I involved profiled autoimmunity using human proteome microarray (HuProt arrays) with 90 serum samples: 40 patients with SSc, 30 patients diagnosed with autoimmune diseases, and 20 healthy subjects. In Phase II, we constructed a focused array with candidates identified antigens and used this to profile a much larger cohort comprised of serum samples. Finally, we used a western blot analysis to validate the serum of validated proteins with high signal values. Bioinformatics analysis allowed us to identify 113 candidate autoantigens that were significantly associated with SSc. This two-phase strategy allowed us to identify and validate anti-small nuclear ribonucleoprotein polypeptide A (SNRPA) as a novel SSc-specific serological biomarker. The observed positive rate of anti-SNRPA antibody in patients with SSc was 11.25%, which was significantly higher than that of any disease control group (3.33%) or healthy controls (1%). In conclusion, anti-SNRPA autoantibody serves as a novel biomarker for SSc diagnosis and may be promising for clinical applications.
