RESUMO
In the field, necrosis area induced by pathogens is usually surrounded by a red circle in apple fruits. However, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we demonstrated that accumulated salicylic acid (SA) induced by fungal infection promoted anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module in apple (Malus domestica). Inoculating apple fruits with Valsa mali or Botryosphaeria dothidea induced a red circle surrounding the necrosis area, which mimicked the phenotype observed in the field. The red circle accumulated a high level of anthocyanins, which was positively correlated with SA accumulation stimulated by fungal invasion. Further analysis showed that SA promoted anthocyanin biosynthesis in a dose-dependent manner in both apple calli and fruits. We next demonstrated that MdNPR1, a master regulator of SA signaling, positively regulated anthocyanin biosynthesis in both apple and Arabidopsis. Moreover, MdNPR1 functioned as a co-activator to interact with and enhance the transactivation activity of MdTGA2.2, which could directly bind to the promoters of anthocyanin biosynthetic and regulatory genes to promote their transcription. Suppressing expression of either MdNPR1 or MdTGA2.2 inhibited coloration of apple fruits, while overexpressing either of them significantly promoted fruit coloration. Finally, we revealed that silencing either MdNPR1 or MdTGA2.2 in apple fruits repressed SA-induced fruit coloration. Therefore, our data determined that fungal-induced SA promoted anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module, resulting in a red circle surrounding the necrosis area in apple fruits.
Assuntos
Antocianinas , Ascomicetos , Frutas , Regulação da Expressão Gênica de Plantas , Malus , Doenças das Plantas , Proteínas de Plantas , Ácido Salicílico , Malus/microbiologia , Malus/genética , Malus/metabolismo , Ácido Salicílico/metabolismo , Antocianinas/biossíntese , Antocianinas/metabolismo , Ascomicetos/fisiologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Frutas/microbiologia , Frutas/metabolismo , Frutas/genética , Arabidopsis/microbiologia , Arabidopsis/genética , Arabidopsis/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
Perovskite light-emitting diodes (PeLEDs) based on CsPb(Br/I)3 nanocrystals (NCs) usually suffer from severe spectral instability under operating voltage due to the poor-quality PeNCs. Herein, zeolite was utilized to prepare high-quality CsPb(Br/I)3 NCs via promoting the homogeneous nucleation and growth and suppressing the Ostwald ripening of PeNCs. In addition, the decomposed zeolite interacted strongly with PeNCs through Pb-O bonds and hydrogen bonds, which inhibited the formation of defects and suppressed halide ion migration, leading to an improved photoluminescence quantum yield (PLQY) and enhanced stability of PeNCs. Moreover, the strong binding affinity of decomposed zeolite to PeNCs contributed to the formation of homogeneous perovskite films with high PLQY. As a result, pure-red PeLEDs with Commission International de I'Eclairage (CIE) coordinates of (0.705, 0.291) were fabricated, approaching the Rec. 2020 red primary color. The devices achieved a peak external quantum efficiency of 23.0% and outstanding spectral stability.
RESUMO
While quasi-two-dimensional (quasi-2D) perovskites have good properties of cascade energy transfer, high exciton binding energy, and high quantum efficiency, which will benefit high-efficiency blue PeLEDs, inefficient domain distribution management and unbalanced carrier transport impede device performance improvement. Herein, (2-(9H-carbazol-9-yl)ethyl)phosphonic acid (2PACz) and methyl 2-aminopyridine-4-carboxylate (MAC) were simultaneously introduced to a blue quasi-2D perovskite film. Relying on the synergistic effect of 2PACz and MAC, it not only modulates the phase distribution inhibiting the n = 2 phase but also greatly improves the electrical property of the quasi-2D perovskite film. As a result, the as-modified blue quasi-2D PeLED demonstrated an external quantum efficiency (EQE) of 17.08% and a luminance of 10142 cd m-2. This study exemplifies the synergistic effect among dual additives and offers a new effective additive strategy modulating phase distribution and building balanced carrier transport, which paves the way for the fabrication of highly efficient blue PeLEDs.
RESUMO
Metal nanoclusters (NCs) hold great promise for expressing multipeak emission based on their well-defined total structure with diverse luminescent centers. Herein, we report the surface motif-dictated triple phosphorescence of Au NCs with dynamic color turning. The deprotonation-triggered isomerization of terminal thiouracils can evolve into a mutual transformation among their hierarchical motifs, thus serving a multipeak-emission expression with good tailoring. More importantly, the underlying electron transfer is thoroughly identified by excluding the radiative and nonradiative energy transfer, where electrons flow from the first phosphorescent state to the last two ones. The findings shed light on finely tailing motifs at the molecular level to motivate studies on customizable luminescence characteristics of metal NCs.
RESUMO
The ternary strategy is one of the effective methods to regulate the morphology of the active layer in organic solar cells (OSCs). In this work, the ternary OSCs with bulk heterojunction (BHJ) or layer-by-layer (LbL) active layers are prepared by using the polymer donor PM6 and the non-fullerene acceptor L8-BO as the main system and the fullerene acceptor PC71BM as the third component. The power conversion efficiencies (PCEs) of BHJ OSCs and LbL OSCs are increased from 17.10% to 18.02% and from 17.20% to 18.20% by introducing PC71BM into the binary active layer, respectively. The in situ UV-vis absorption spectra indicate that the molecular aggregation and crystallization process can be prolonged by introducing PC71BM into the PM6:L8-BO or PM6/L8-BO active layer. The molecular orientation and molecular crystallinity in the active layer are optimized by introducing the PC71BM into the binary BHJ or LbL active layers, which can be confirmed by the experimental results of grazing incidence wide-angle X-ray scattering. This study demonstrates that the third component PC71BM can be used as a morphology regulator to regulate the morphology of BHJ or LbL active layers, thus effectively improving the performance of BHJ and LbL OSCs.
RESUMO
The morphology of the active layer is crucial for highly efficient organic solar cells (OSCs), which can be regulated by selecting a rational third component. In this work, the highly crystalline nonfullerene acceptor BTP-eC9 is selected as the morphology regulator in OSCs with PM6:BTP-BO-4Cl as the main system. The addition of BTP-eC9 can prolong the nucleation and crystallization progress of acceptor and donor molecules, thereby enhancing the order of molecular arrangement. Meanwhile, the nucleation and crystallization time of the donor is earlier than that of the acceptors after introducing BTP-eC9, which is beneficial for obtaining a better vertical structural phase separation. The exciton dissociation, charge transport, and charge collection are promoted effectively by the optimized morphology of the active layer, which improves the short-circuit current density and filling factor. After introducing BTP-eC9, the power conversion efficiencies (PCEs) of the ternary OSCs are improved from 17.31% to 18.15%. The PCE is further improved to 18.39% by introducing gold nanopyramid (Au NBPs) into the hole transport layer to improve photon utilization efficiency. This work indicates that the morphology can be optimized by selecting a highly crystalline third component to regulate the nucleation and crystallization progress of the acceptor and donor molecules.
RESUMO
Fruit colour is a critical determinant for the appearance quality and commercial value of apple fruits. Viroid-induced dapple symptom severely affects the fruit coloration, however, the underlying mechanism remains unknown. In this study, we identified an apple dimple fruit viroid (ADFVd)-derived small interfering RNA, named vsiR693, which targeted the mRNA coding for a bHLH transcription factor MdPIF1 (PHYTOCHROME-INTERACTING FACTOR 1) to regulate anthocyanin biosynthesis in apple. 5' RLM-RACE and artificial microRNA transient expression system proved that vsiR693 directly targeted the mRNA of MdPIF1 for cleavage. MdPIF1 positively regulated anthocyanin biosynthesis in both apple calli and fruits, and it directly bound to G-box element in the promoter of MdPAL and MdF3H, two anthocyanin biosynthetic genes, to promote their transcription. Expression of vsiR693 negatively regulated anthocyanin biosynthesis in both apple calli and fruits. Furthermore, co-expression of vsiR693 and MdPIF1 suppressed MdPIF1-promoted anthocyanin biosynthesis in apple fruits. Infiltration of ADFVd infectious clone suppressed coloration surrounding the injection sites in apple fruits, while a mutated version of ADFVd, in which the vsiR693 producing region was mutated, failed to repress fruit coloration around the injection sites. These data provide evidence that a viroid-derived small interfering RNA targets host transcription factor to regulate anthocyanin biosynthesis in apple.
RESUMO
Heat shock protein 20 (Hsp20) is a small molecule heat shock protein that plays an important role in plant growth, development, and stress resistance. Little is known about the function of Hsp20 family genes in apple (Malus domestica). Here, we performed a genome-wide analysis of the apple Hsp20 gene family, and a total of 49 Hsp20s genes were identified from the apple genome. Phylogenetic analysis revealed that the 49 genes were divided into 11 subfamilies, and MdHsp18.2b, a member located in the CI branch, was selected as a representative member for functional characterization. Treatment with NaCl and Botryosphaeria dothidea (B. dothidea), the causal agent of apple ring rot disease, significantly induced MdHsp18.2b transcription level. Further analysis revealed that overexpressing MdHsp18.2b reduced the resistance to salt stress but enhanced the resistance to B. dothidea infection in apple calli. Moreover, MdHsp18.2b positively regulated anthocyanin accumulation in apple calli. Physiology assays revealed that MdHsp18.2b promoted H2O2 production, even in the absence of stress factors, which might contribute to its functions in response to NaCl and B. dothidea infection. Hsps usually function as homo- or heterooligomers, and we found that MdHsp18.2b could form a heterodimer with MdHsp17.9a and MdHsp17.5, two members from the same branch with MdHsp18.2b in the phylogenetic tree. Therefore, we identified 49 Hsp20s genes from the apple genome and found that MdHsp18.2b was involved in regulating plant resistance to salt stress and B. dothidea infection, as well as in regulating anthocyanin accumulation in apple calli.
Assuntos
Regulação da Expressão Gênica de Plantas , Proteínas de Choque Térmico HSP20 , Malus , Filogenia , Doenças das Plantas , Proteínas de Plantas , Malus/genética , Malus/microbiologia , Malus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Proteínas de Choque Térmico HSP20/genética , Proteínas de Choque Térmico HSP20/metabolismo , Ascomicetos/fisiologia , Ascomicetos/genética , Ascomicetos/patogenicidade , Família Multigênica , Resistência à Doença/genética , Antocianinas/metabolismoRESUMO
Properties of the underlying hole transport layer (HTL) play a crucial role in determining the optoelectronic performance of perovskite light-emitting devices (PeLEDs). However, endowing the current HTL system with a deep highest occupied molecular orbital (HOMO) level concurrent with high hole mobility is still a big challenge, in particular being an open constraint toward high-efficiency blue PeLEDs. In this regard, employing the poly(9-vinylcarbazole) as a model, we perform efficient incorporation of the atomic-precision metal nanoclusters (NCs), [Ag6PL6, PL = (S)-4-phenylthiazolidine-2-thione], to achieve significant tailoring in both HOMO energy level and hole mobility. As a result, the as-modified PeLEDs exhibit an external quantum efficiency (EQE) of 14.29% at 488 nm. The presented study exemplifies the success of metal NC involved HTL engineering and offers a simple yet effective additive strategy to settle the blue PeLED HTL dilemma, which paves the way for the fabrication of highly efficient blue PeLEDs.
RESUMO
Cesium lead halide perovskite nanocrystals (PNCs) exhibit promising prospects for application in optoelectronic devices. However, electroactivated near-infrared (NIR) PNC light-emitting diodes (LEDs) with emission peaks over 800 nm have not been achieved. Herein, we demonstrate the electroactivated NIR PNC LEDs based on Yb3+-doped CsPb(Cl1-xBrx)3 PNCs with extraordinary high NIR photoluminescence quantum yields over 170%. The fabricated NIR LEDs possess an irradiance of 584.7 µW cm-2, an EQE of 1.2%, and a turn-on voltage of 3.1 V. The ultrafast quantum cutting process from the PNC host to Yb3+ has been revealed as the main mechanism of electroluminescence (EL)-activated Yb3+ for the first time via exploring how the trend between the EL intensity of PNC and Yb3+ varies with different voltages along with the tendency of temperature- and doping-concentration-dependent PL and EL spectra. This work will extend the application of PNCs to optical communication, night-vision devices, and biomedical imaging.
RESUMO
Plants possess the remarkable ability to sense detrimental environmental stimuli and launch sophisticated signal cascades that culminate in tailored responses to facilitate their survival, and transcription factors (TFs) are closely involved in these processes. Phytochrome interacting factors (PIFs) are among these TFs and belong to the basic helix-loop-helix family. PIFs are initially identified and have now been well established as core regulators of phytochrome-associated pathways in response to the light signal in plants. However, a growing body of evidence has unraveled that PIFs also play a crucial role in adapting plants to various biological and environmental pressures. In this review, we summarize and highlight that PIFs function as a signal hub that integrates multiple environmental cues, including abiotic (i.e., drought, temperature, and salinity) and biotic stresses to optimize plant growth and development. PIFs not only function as transcription factors to reprogram the expression of related genes, but also interact with various factors to adapt plants to harsh environments. This review will contribute to understanding the multifaceted functions of PIFs in response to different stress conditions, which will shed light on efforts to further dissect the novel functions of PIFs, especially in adaption to detrimental environments for a better survival of plants.
Assuntos
Proteínas de Arabidopsis , Fitocromo , Fitocromo/genética , Fitocromo/metabolismo , Proteínas de Arabidopsis/genética , Transdução de Sinais/genética , Regulação da Expressão Gênica de Plantas , Plantas/genética , Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismoRESUMO
Although colloidal perovskite nanocrystal (PNC) solution has exhibited near-unity photoluminescence quantum yield (PLQY), the luminance would be severely quenched when the PNC solution is assembled into thin films due to the agglomeration and fusion of NCs caused by the exfoliation of surface ligands and non-radiative Förster resonance energy transfer (FRET) from small to large particle sizes, which seriously affected the performances of light-emitting diodes (LEDs). Here, we used Guanidine thiocyanate (GASCN) and Sodium thiocyanate (NaSCN) to achieve effective CsPbI3 PNC surface reconstruction. Due to the strong coordination ability of these small molecules with the anions and cations on the surface of the PNCs, they can provide strong surface protection against PNC fusion during centrifugal purification process and repair the surface defects of PNCs, so that the original uniform size distribution of PNCs can be maintained and FRET between close-packed PNC films is effectively suppressed, which allows the emission characteristics of the films to be preserved. As a result, highly oriented, smooth and nearly defect-free high-quality PNC thin films are obtained, with PLQY as high as 95.1 %, far exceeding that of the original film, and corresponding LEDs exhibit a maximum external quantum efficiency of 24.5 %.
RESUMO
An 18-protein multiple sclerosis (MS) disease activity (DA) test was validated based on associations between algorithm scores and clinical/radiographic assessments (N = 614 serum samples; Train [n = 426; algorithm development] and Test [n = 188; evaluation] subsets). The multi-protein model was trained based on presence/absence of gadolinium-positive (Gd+) lesions and was also strongly associated with new/enlarging T2 lesions, and active versus stable disease (composite of radiographic and clinical evidence of DA) with improved performance (p < 0.05) compared to the neurofilament light single protein model. The odds of having ≥1 Gd+ lesions with a moderate/high DA score were 4.49 times that of a low DA score, and the odds of having ≥2 Gd+ lesions with a high DA score were 20.99 times that of a low/moderate DA score. The MSDA Test was clinically validated with improved performance compared to the top-performing single-protein model and can serve as a quantitative tool to enhance the care of MS patients.
Assuntos
Esclerose Múltipla , Humanos , Imageamento por Ressonância Magnética , Proteínas Sanguíneas , Gadolínio , AlgoritmosRESUMO
Perovskite solar cells (PSCs) based on 2D/3D composite structure have shown enormous potential to combine high efficiency of 3D perovskite with high stability of 2D perovskite. However, there are still substantial non-radiative losses produced from trap states at grain boundaries or on the surface of conventional 2D/3D composite structure perovskite film, which limits device performance and stability. In this work, a multifunctional magnetic field-assisted interfacial embedding strategy is developed to construct 2D/3D composite structure. The composite structure not only improves crystallinity and passivates defects of perovskite layer, but also can efficiently promote vertical hole transport and provide lateral barrier effect. Meanwhile, the composite structure also forms a good surface and internal encapsulation of 3D perovskite to inhibit water diffusion. As a result, the multifunctional effect effectively improves open-circuit voltage and fill factor, reaching maximum values of 1.246 V and 81.36%, respectively, and finally achieves power conversion efficiency (PCE) of 24.21%. The unencapsulated devices also demonstrate highly improved long-term stability and humidity stability. Furthermore, an augmented performance of 21.23% is achieved, which is the highest PCE of flexible device based on 2D/3D composite perovskite films coupled with the best mechanical stability due to the 2D/3D alternating structure.
RESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)-derived from exons 2-6 of EYA3-facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions. METHODS: CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model. RESULTS: CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells. CONCLUSIONS: Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.
RESUMO
Pulmonary inflammation involves complex changes of the immune cells, in which macrophages play important roles and their function might be influenced by metabolism. Slc38a6 acts as a carrier of nutrient for macrophages (Mφ) to exert the function. In this study, pneumonia patient blood was found up-regulated SLC38A6 expression, which correlated with monocytes number and white blood cell number. The similar result was also shown in LPS induced sepsis mice. To reveal the key role of Slc38a6, we used systemic and conditional knock-out mice. Either systemic or LyzCRE specific knock-out could alleviate the severity of sepsis mice, reduce the proinflammatory cytokine TNF-α and IL-1ß expression in serum and decrease the monocytes number in bronchial alveolar lavage and peritoneal lavage via flow cytometry. In order to reveal the signal of up-regulated Slc38a6, the Tlr4 signal inhibitor TAK242 and TLR4 knock-out mice were used. By blocking Tlr4 signal in macrophages via TAK242, the expression of Slc38a6 was down-regulated synchronously, and the same results were also found in Tlr4 knock-out macrophages. However, in the overexpressed Slc38a6 macrophages, blocking Tlr4 signal via TAK242, 20% of the mRNA expression of IL-1ß still could be expressed, indicating that up-regulated Slc38a6 participates in IL-1ß expression process. Collectively, it is the first time showed that an amino acid transporter SLC38A6 up-regulated in monocytes/macrophages promotes activation in pulmonary inflammation. SLC38A6 might be a promising target molecule for pulmonary inflammation treatment.
Assuntos
Pneumonia , Receptor 4 Toll-Like , Animais , Camundongos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/metabolismo , Camundongos Knockout , Pneumonia/induzido quimicamente , Pneumonia/genética , Pneumonia/metabolismo , Transdução de Sinais/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Sistemas de Transporte de Aminoácidos Neutros/metabolismoRESUMO
Reasonable fertilization management can increase nutrient content and enzyme activity in rhizosphere soil, and even increase soil microbial richness. However, different fertilizers could raise distinct influences on the soil properties, including soil environmental factors (physicochemical properties and enzymatic activities) and microbial community. Here, the effects of two soil amendments (microbial fertilizer and woody peat) on environmental factors and microbial community structure in tobacco rhizosphere soil were evaluated, with the correlations between microbes and environmental factors explored. As the results, microbial fertilizer could effectively alleviate soil acidification, increase available potassium and organic matter contents in soil, and was also beneficial to increase nitrate reductase activity in rhizosphere soil. Fertilizers cause changes in the abundance of certain microbes in the soil. Besides, it was shown that the candidate phyla Gal15, Acidobacterota, Latescibacterota, Mortierellommycota, Basidiomycota, and Rozellomycota in tobacco rhizosphere soil had significant correlation with soil environmental factors. Through the functional analysis of these populations, it can be deduced that the changes in the abundance of certain microorganisms may be an important reason for the differences in environmental factors. All these indicated that the differences of environmental factors in different treatments are closely related to the abundance of some special soil microorganisms. Studying the life activities of these microbes would provide good guidance for exploring the interaction among crops, soil, and microorganisms and improving crop yields.
Assuntos
Fertilizantes , Solo , Solo/química , Fertilizantes/análise , Nicotiana , Rizosfera , Microbiologia do SoloRESUMO
Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.
Assuntos
Malus , Malus/microbiologia , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Proteínas de Plantas/metabolismo , Doenças das Plantas/microbiologia , Chá/metabolismoRESUMO
Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic biomarkers, or therapeutic targets. However, the exact mechanisms of lncRNAs in the regulation of OA progression remain unclear. In the present study, the lncRNA WDR11 divergent transcript (lncRNA WDR11-AS1) was shown to be downregulated in osteoarthritic cartilage tissues from patients, and to promote extracellular matrix (ECM) synthesis in osteoarthritic chondrocytes with knockdown and overexpression experiments. This function of lncRNA WDR11-AS1 was linked to its ability to interact with the polyadenylate-binding protein cytoplasmic 1 (PABPC1), which was screened by RNA pulldown and mass spectrometry analyses. PABPC1 was discovered to bind ECM-related mRNAs such as SOX9, and the inhibition of PABPC1 improved the mRNA stability of SOX9 to mitigate OA progression. Our results suggest that lncRNA WDR11-AS1 has a promising inhibitory effect on inflammation-induced ECM degradation in OA by directly binding PABPC1, thereby establishing lncRNA WDR11-AS1 and PABPC1 as potential therapeutic targets in the treatment of OA.
Assuntos
Cartilagem Articular , MicroRNAs , Osteoartrite , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , Osteoartrite/genética , Osteoartrite/metabolismo , Condrócitos/metabolismo , Matriz Extracelular/metabolismo , Cartilagem Articular/metabolismo , Inflamação/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismoRESUMO
MicroRNA-147 (miR-147) had been previously found induced in synoviocytes by inflammatory stimuli derived from T cells in experimental arthritis. This study was designed to verify whether loss of its function might alleviate inflammatory events in joints of experimental and rheumatoid arthritis (RA). Dark Agouti (DA) rats were injected intradermally with pristane to induce arthritis, and rno-miR-147 antagomir was locally administrated into individual ankle compared with negative control or rno-miR-155-5p antagomir (potential positive control). Arthritis onset, macroscopic severity, and pathological changes were monitored. While in vitro, gain or loss function of hsa-miR-147b-3p/hsa-miR-155-5p and ZNF148 was achieved in human synovial fibroblast cell line SW982 and RA synovial fibroblasts (RASF). The expression of miRNAs and mRNAs was detected by using RT-quantitative PCR, and protein expression was detected by using Western blotting. Anti-miR-147 therapy could alleviate the severity, especially for the synovitis and joint destruction in experimental arthritis. Gain of hsa-miR-147b-3p/hsa-miR-155-5p function in TNF-α stimulated SW982 and RASF cells could upregulate, in contrast, loss of hsa-miR-147b-3p/hsa-miR-155-5p function could downregulate the gene expression of TNF-α, IL-6, MMP3, and MMP13. Hence, such alteration could participate in synovial inflammation and joint destruction. RNAi of ZNF148, a miR-147's target, increased gene expression of TNF-α, IL-6, MMP3, and MMP13 in SW982 and RASF cells. Also, mRNA sequencing data showed that hsa-miR-147b-3p mimic and ZNF148 siRNA commonly regulated the gene expression of CCL3 and DEPTOR as well as some arthritis and inflammation-related pathways. Taken together, miR-147b-3p contributes to synovial inflammation through repressing ZNF148 in RA and experimental arthritis.