KLF transcription factors in bone diseases.

Krüppel-like factors (KLFs) are crucial in the development of bone disease. They are a family of zinc finger transcription factors that are unusual in containing three highly conserved zinc finger structural domains interacting with DNA. It has been discovered that it engages in various cell functions, including proliferation, apoptosis, autophagy, stemness, invasion and migration, and is crucial for the development of human tissues. In recent years, the role of KLFs in bone physiology and pathology has received adequate attention. In addition to regulating the normal growth and development of the musculoskeletal system, KLFs participate in the pathological process of the bones and joints and are intimately linked to several skeletal illnesses, such as osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP) and osteosarcoma (OS). Consequently, targeting KLFs has emerged as a promising therapeutic approach for an array of bone disorders. In this review, we summarize the current literature on the importance of KLFs in the emergence and regulation of bone illnesses, with a particular emphasis on the pertinent mechanisms by which KLFs regulate skeletal diseases. We also discuss the need for KLFs-based medication-targeted treatment. These endeavours offer new perspectives on the use of KLFs in bone disorders and provide prognostic biomarkers, therapeutic targets and possible drug candidates for bone diseases.

G-quadruplex inducer/stabilizer pyridostatin targets SUB1 to promote cytotoxicity of a transplatinum complex.

Pyridostatin (PDS) is a well-known G-quadruplex (G4) inducer and stabilizer, yet its target genes have remained unclear. Herein, applying MS proteomics strategy, we revealed PDS significantly downregulated 22 proteins but upregulated 16 proteins in HeLa cancer cells, of which the genes both contain a number of G4 potential sequences, implying that PDS regulation on gene expression is far more complicated than inducing/stabilizing G4 structures. The PDS-downregulated proteins consequently upregulated 6 proteins to activate cyclin and cell cycle regulation, suggesting that PDS itself is not a potential anticancer agent, at least toward HeLa cancer cells. Importantly, SUB1, which encodes human positive cofactor and DNA lesion sensor PC4, was downregulated by 4.76-fold. Further studies demonstrated that the downregulation of PC4 dramatically promoted the cytotoxicity of trans-[PtCl2(NH3)(thiazole)] (trans-PtTz) toward HeLa cells to a similar level of cisplatin, contributable to retarding the repair of 1,3-trans-PtTz crosslinked DNA lesion mediated by PC4. These findings not only provide new insights into better understanding on the biological functions of PDS but also implicate a strategy for the rational design of novel multi-targeting platinum anticancer drugs via conjugation of PDS as a ligand to the coordination scaffold of transplatin for battling drug resistance to cisplatin.

Potential Targets of Natural Products for Improving Cardiac Ischemic Injury: The Role of Nrf2 Signaling Transduction.

Myocardial ischemia is the leading cause of health loss from cardiovascular disease worldwide. Myocardial ischemia and hypoxia during exercise trigger the risk of sudden exercise death which, in severe cases, will further lead to myocardial infarction. The Nrf2 transcription factor is an important antioxidant regulator that is extensively engaged in biological processes such as oxidative stress, inflammatory response, apoptosis, and mitochondrial malfunction. It has a significant role in the prevention and treatment of several cardiovascular illnesses, since it can control not only the expression of several antioxidant genes, but also the target genes of associated pathological processes. Therefore, targeting Nrf2 will have great potential in the treatment of myocardial ischemic injury. Natural products are widely used to treat myocardial ischemic diseases because of their few side effects. A large number of studies have shown that the Nrf2 transcription factor can be used as an important way for natural products to alleviate myocardial ischemia. However, the specific role and related mechanism of Nrf2 in mediating natural products in the treatment of myocardial ischemia is still unclear. Therefore, this review combs the key role and possible mechanism of Nrf2 in myocardial ischemic injury, and emphatically summarizes the significant role of natural products in treating myocardial ischemic symptoms, thus providing a broad foundation for clinical transformation.

Phytochemicals against Osteoarthritis by Inhibiting Apoptosis.

Osteoarthritis (OA) is a chronic joint disease that causes pathological changes in articular cartilage, synovial membrane, or subchondral bone. Conventional treatments for OA include surgical and non-surgical methods. Surgical treatment is suitable for patients in the terminal stage of OA. It is often the last choice because of the associated risks and high cost. Medication of OA mainly includes non-steroidal anti-inflammatory drugs, analgesics, hyaluronic acid, and cortico-steroid anti-inflammatory drugs. However, these drugs often have severe side effects and cannot meet the needs of patients. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Apoptosis is programmed cell death, which is a kind of physiologic cell suicide determined by heredity and conserved by evolution. Inhibition of apoptosis-related pathways has been found to prevent and treat a variety of diseases. Excessive apoptosis can destroy cartilage homeostasis and aggravate the pathological process of OA. Therefore, inhibition of apoptosis-related factors or signaling pathways has become an effective means to treat OA. Phytochemicals are active ingredients from plants, and it has been found that phytochemicals can play an important role in the prevention and treatment of OA by inhibiting apoptosis. We summarize preclinical and clinical studies of phytochemicals for the treatment of OA by inhibiting apoptosis. The results show that phytochemicals can treat OA by targeting apoptosis-related pathways. On the basis of improving some phytochemicals with low bioavailability, poor water solubility, and high toxicity by nanotechnology-based drug delivery systems, and at the same time undergoing strict clinical and pharmacological tests, phytochemicals can be used as a potential therapeutic drug for OA and may be applied in clinical settings.

Trichostatin A Promotes Cytotoxicity of Cisplatin, as Evidenced by Enhanced Apoptosis/Cell Death Markers.

Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, promotes the cytotoxicity of the genotoxic anticancer drug cisplatin, yet the underlying mechanism remains poorly understood. Herein, we revealed that TSA at a low concentration (1 µM) promoted the cisplatin-induced activation of caspase-3/6, which, in turn, increased the level of cleaved PARP1 and degraded lamin A&C, leading to more cisplatin-induced apoptosis and G2/M phase arrest of A549 cancer cells. Both ICP-MS and ToF-SIMS measurements demonstrated a significant increase in DNA-bound platinum in A549 cells in the presence of TSA, which was attributable to TSA-induced increase in the accessibility of genomic DNA to cisplatin attacking. The global quantitative proteomics results further showed that in the presence of TSA, cisplatin activated INF signaling to upregulate STAT1 and SAMHD1 to increase cisplatin sensitivity and downregulated ICAM1 and CD44 to reduce cell migration, synergistically promoting cisplatin cytotoxicity. Furthermore, in the presence of TSA, cisplatin downregulated TFAM and SLC3A2 to enhance cisplatin-induced ferroptosis, also contributing to the promotion of cisplatin cytotoxicity. Importantly, our posttranslational modification data indicated that acetylation at H4K8 played a dominant role in promoting cisplatin cytotoxicity. These findings provide novel insights into better understanding the principle of combining chemotherapy of genotoxic drugs and HDAC inhibitors for the treatment of cancers.

Strophanthidin Induces Apoptosis of Human Lung Adenocarcinoma Cells by Promoting TRAIL-DR5 Signaling.

Strophanthidin (SPTD), one of the cardiac glycosides, is refined from traditional Chinese medicines such as Semen Lepidii and Antiaris toxicaria, and was initially used for the treatment of heart failure disease in clinic. Recently, SPTD has been shown to be a potential anticancer agent, but the underlying mechanism of action is poorly understood. Herein, we explored the molecular mechanism by which SPTD exerts anticancer effects in A549 human lung adenocarcinoma cells by means of mass spectrometry-based quantitative proteomics in combination with bioinformatics analysis. We revealed that SPTD promoted the expression of tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2, or DR5) in A549 cells to activate caspase 3/6/8, in particular caspase 3. Consequently, the activated caspases elevated the expression level of apoptotic chromatin condensation inducer in the nucleus (ACIN1) and prelamin-A/C (LMNA), ultimately inducing apoptosis via cooperation with the SPTD-induced overexpressed barrier-to-autointegration factor 1 (Banf1). Moreover, the SPTD-induced DEPs interacted with each other to downregulate the p38 MAPK/ERK signaling, contributing to the SPTD inhibition of the growth of A549 cells. Additionally, the downregulation of collagen COL1A5 by SPTD was another anticancer benefit of SPTD through the modulation of the cell microenvironment.

A Photoactivated Ru (II) Polypyridine Complex Induced Oncotic Necrosis of A549 Cells by Activating Oxidative Phosphorylation and Inhibiting DNA Synthesis as Revealed by Quantitative Proteomics.

The ruthenium polypyridine complex [Ru(dppa)2(pytp)] (PF6)2 (termed as ZQX-1), where dppa = 4,7-diphenyl-1,10-phenanthroline and pytp = 4'-pyrene-2,2':6',2''-terpyridine, has been shown a high and selective cytotoxicity to hypoxic and cisplatin-resistant cancer cells either under irradiation with blue light or upon two-photon excitation. The IC50 values of ZQX-1 towards A549 cancer cells and HEK293 health cells are 0.16 ± 0.09 µM and >100 µM under irradiation at 420 nm, respectively. However, the mechanism of action of ZQX-1 remains unclear. In this work, using the quantitative proteomics method we identified 84 differentially expressed proteins (DEPs) with |fold-change| ≥ 1.2 in A549 cancer cells exposed to ZQX-1 under irradiation at 420 nm. Bioinformatics analysis of the DEPs revealed that photoactivated ZQX-1 generated reactive oxygen species (ROS) to activate oxidative phosphorylation signaling to overproduce ATP; it also released ROS and pyrene derivative to damage DNA and arrest A549 cells at S-phase, which synergistically led to oncotic necrosis and apoptosis of A549 cells to deplete excess ATP, evidenced by the elevated level of PRAP1 and cleaved capase-3. Moreover, the DNA damage inhibited the expression of DNA repair-related proteins, such as RBX1 and GPS1, enhancing photocytotoxicity of ZQX-1, which was reflected in the inhibition of integrin signaling and disruption of ribosome assembly. Importantly, the photoactivated ZQX-1 was shown to activate hypoxia-inducible factor 1A (HIF1A) survival signaling, implying that combining use of ZQX-1 with HIF1A signaling inhibitors may further promote the photocytotoxicity of the prodrug.

Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells.

Cancer stem cells drive tumor initiation, progression, and recurrence, which compromise the effectiveness of anti-tumor drugs. Here, we report that demethylzeylasteral (DML), a triterpene anti-tumor compound, suppressed tumorigenesis of liver cancer stem cells (LCSCs) by interfering with lactylation of a metabolic stress-related histone. Using RNA sequencing (RNA-seq) and gas chromatography-mass spectrometric (GC-MS) analysis, we showed that the glycolysis metabolic pathway contributed to the anti-tumor effects of DML, and then focused on lactate downstream regulation as the molecular target. Mechanistically, DML opposed the progress of hepatocellular carcinoma (HCC), which was efficiently facilitated by the increase in H3 histone lactylation. Two histone modification sites: H3K9la and H3K56la, which were found to promote tumorigenesis, were inhibited by DML. In addition, we used a nude mouse tumor xenograft model to confirm that the anti-liver cancer effects of DML are mediated by regulating H3 lactylation in vivo. Our findings demonstrate that DML suppresses the tumorigenicity induced by LCSCs by inhibiting H3 histone lactylation, thus implicating DML as a potential candidate for the supplementary treatment of hepatocellular carcinoma.

Step-by-Step Assembly of Metal-Organic Frameworks from Trinuclear Cu3 Clusters.

Two novel metal-organic frameworks (MOFs), HBNU-1 and HBNU-2, have been synthesized successfully. We adopt a step-by-step assembly strategy, which first synthesize the Cu3 cluster Cu3(µ3-OH)(pz)3(CH3COO)2(Hpz), and then react it with H2BDC under different conditions to form final frameworks. In both MOF structures, the Cu3 clusters are maintained, although certain differences are observed. Compared with HBNU-1, the Cu3 cluster dimerizes into Cu6 cluster in HBNU-2. With this step-by-step cluster assembly strategy, MOF structure predicting becomes possible and may give some reference for MOF structure designing.

miR-23b Suppresses Leukocyte Migration and Pathogenesis of Experimental Autoimmune Encephalomyelitis by Targeting CCL7.

MicroRNAs (miRNAs) are small, non-coding RNAs involved in immune response regulation. Specific miRNAs have been linked to the development of various autoimmune diseases; however, their contribution to the modulation of CNS-directed cellular infiltration remains unclear. In this study, we found that miR-23b, in addition to its reported functions in the suppression of IL-17-associated autoimmune inflammation, halted the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by directly inhibiting the migration of pathogenic leukocytes to the CNS. We demonstrated that miR-23b was specifically decreased during the acute phase of EAE and that overexpression of miR-23b resulted in a defect in leukocyte migration and strong resistance to EAE. Furthermore, we found that miR-23b suppressed leukocyte migration of EAE by targeting CCL7, a chemokine that attracts monocytes during inflammation and metastasis. Finally, in the adoptive transfer model, miR-23b reduced the severity of EAE by inhibiting the migration of pathogenic T cells to the CNS rather than diminishing the encephalitogenesis of T cells. Taken together, our results characterize a novel aspect of miR-23b function in leukocyte migration, and they identify miR-23b as a potential therapeutic target in the amelioration of MS and likely other autoimmune diseases.

Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry.

The clinically widely-used anticancer drug, cisplatin, binds strongly to DNA as a DNA-damaging agent. Herein, we investigated the interaction of cisplatin with a 15-mer single-stranded C,T-rich oligodeoxynucleotide, 5'-CCTT4CTT7G8C9T10TCTCC-3' (ODN15), using ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) in conjunction with tandem mass spectrometry (top-down MS). Top-down MS analysis with collision-induced dissociation (CID) fragmentation of the mono-platinated and di-platinated ODN15 provided abundant and informative Pt-containing or Pt-free a/[a - B], w and internal fragments, allowing the unambiguous identification of T4, T7, C9, and T10 as the platination sites on the cisplatin-ODN15 adducts. These results revealed that, in addition to the well-established guanine site, the unexpected thermodynamic binding of cisplatin to cytosine and thymine bases was also evident at the oligonucleotide level. Furthermore, the binding models of cisplatin with cytosine and thymine bases were built as the Pt coordinated to cytosine-N(3) and thymine-N(3) with displacement of the proton or tautomerization of thymine. These findings contribute to a better understanding of the mechanism of action of cisplatin and its preference for gene loci when the drug binds to cellular DNA, and also demonstrate the great potential and superiority of FT-ICR MS in studying the interactions of metallodrugs with large biomolecules.

Grazing effects on surface energy fluxes in a desert steppe on the Mongolian Plateau.

Quantifying the surface energy fluxes of grazed and ungrazed steppes is essential to understand the roles of grasslands in local and global climate and in land use change. We used paired eddy-covariance towers to investigate the effects of grazing on energy balance (EB) components: net radiation (Rn ), latent heat (LE), sensible heat (H), and soil heat (G) fluxes on adjacent grazed and ungrazed areas in a desert steppe of the Mongolian Plateau for a two-year period (2010-2012). Near 95% of Rn was partitioned as LE and H, whereas the contributions of G and other components of the EB were 5% at an annual scale. H dominated the energy partitioning and shared ~50% of Rn . When comparing the grazed and the ungrazed desert steppe, there was remarkably lower Rn and a lower H, but higher G at the grazed site than at the ungrazed site. Both reduced available energy (Rn - G) and H indicated a "cooling effect" feedback onto the local climate through grazing. Grazing reduced the dry year LE but enhanced the wet year LE. Energy partitioning of LE/Rn was positively correlated with the canopy conductivity, leaf area index, and soil moisture. H/Rn was positively correlated with the vapor pressure deficit but negatively correlated with the soil moisture. Boosted regression tree results showed that LE/Rn was dominated by soil moisture in both years and at both sites, while grazing shifted the H/Rn domination from temperature to soil moisture in the wet year. Grazing not only caused an LE shift between the dry and the wet year, but also triggered a decrease in the H/Rn because of changes in vegetation and soil properties, indicating that the ungrazed area had a greater resistance while the grazed area had a greater sensitivity of EB components to the changing climate.

Hydrogen-peroxide-modified egg albumen for transparent and flexible resistive switching memory.

Egg albumen is modified by hydrogen peroxide with concentrations of 5%, 10%, 15% and 30% at room temperature. Compared with devices without modification, a memory cell of Ag/10% H2O2-egg albumen/indium tin oxide exhibits obviously enhanced resistive switching memory behavior with a resistance ratio of 104, self-healing switching endurance for 900 cycles and a prolonged retention time for a 104 s @ 200 mV reading voltage after being bent 103 times. The breakage of massive protein chains occurs followed by the recombination of new protein chain networks due to the oxidation of amidogen and the synthesis of disulfide during the hydrogen peroxide modifying egg albumen. Ions such as Fe3+, Na+, K+, which are surrounded by protein chains, are exposed to the outside of protein chains to generate a series of traps during the egg albumen degeneration process. According to the fitting results of the double logarithm I-V curves and the current-sensing atomic force microscopy (CS-AFM) images of the ON and OFF states, the charge transfer from one trap center to its neighboring trap center is responsible for the resistive switching memory phenomena. The results of our work indicate that hydrogen- peroxide-modified egg albumen could open up a new avenue of biomaterial application in nanoelectronic systems.

Cereus sinensis Polysaccharide and Its Immunomodulatory Properties in Human Monocytic Cells.

In this study, the extraction conditions of the crude polysaccharide from Cereus sinensis were optimized by response surface methodology. The optimum extraction conditions were: a ratio of raw material to water volume of 1:80 (g/mL); an extraction temperature of 72 °C; and an extraction time of 3 h. Then, a purified polysaccharide named Cereus sinensis polysaccharide-1 (CSP-1) was obtained from the crude polysaccharide by the Diethylaminoethyl cellulose-52 (DEAE-52) cellulose chromatography column and Sephadex G-100 column. The molecular weight and monosaccharide composition of CSP-1 was determined through Gel Permeation Chromatography (GPC) and Gas Chromatography-Mass Spectrometer (GS-MS), respectively. The results showed that CSP-1 with an average molecular weight of 56,335 Da was composed of l-(-)-Fucose, d-(+)-Mannose, d-Glucose and mainly possessed 1→2, 1→2, 6, 1→4, and 1→4, 6 of glycosyl linkages. The immunomodulatory activities of CSP-1 were also evaluated using lipopolysaccharide (LPS)-induced human monocytic (THP-1) cells. The results demonstrated that CSP-1 dose-dependently protected against LPS-induced toxicity, and CSP-1 significantly inhibited the Toll-like receptor 4 (TLR-4) mRNA, myeloid differentiation factor 88 (MyD88) mRNA and tumour necrosis factor receptor-associated factor-6 (TRAF-6) mRNA expression of the LPS-induced THP-1 cells, as well as suppressing reactive oxygen species (ROS) generation.

The further characterization of the peptide specifically binding to gastric cancer.

Targeting peptide has been considered to be useful as a small molecule probe leading to multifunctional properties for both imaging detection and targeting therapy. Thus, the identification of novel targets is urgently needed to develop innovative agents to effectively control gastric cancer metastasis and progression. Previously, we reported a novel 12-mer peptide, GP-5 (IHKDKNAPSLVP), binding to gastric carcinoma (GC) cells specifically and sensitively, and it was screened by using a phage displayed peptide library and primarily analyzed. In this study, it was further identified via fluorescence microscopy, flow cytometry, tissue chip and other methods. Our results indicated that the peptide GP-5 presents a particularly high affinity and specificity to GC cells and tissues, whereas only background detection occurred with other control cancer cells, cancer tissues or normal tissues. Taken together, all results support that the peptide GP-5 is a potential candidate to be developed as a useful molecule fragment for the imaging detection and targeting therapy of GC.

The effects of grazing and watering on ecosystem CO2 fluxes vary by community phenology.

Grazing profoundly influences vegetation and the subsequent carbon fluxes in various ecosystems. However, little effort has been made to explore the underlying mechanisms for phenological changes and their consequences on carbon fluxes at ecosystem level, especially under the coupled influences of human disturbances and climate change. Here, a manipulative experiment (2012-2013) was conducted to examine both the independent and interactive effects of grazing and watering on carbon fluxes across phenological phases in a desert steppe. Grazing advanced or delayed phenological timing, leading to a shortened green-up phase (GrP: 23.60 days) in 2013 and browning phase (BrP: 12.48 days) in 2012 from high grazing, and insignificant effects on the reproductive phase (ReP) in either year. High grazing significantly enhance carbon uptake, while light grazing reduce carbon uptake in ReP. Watering only delayed the browning time by 5.01 days in 2013, producing no significant effects on any phenophase. Watering promoted the net ecosystem exchange (NEE), ecosystem respiration (ER), and gross ecosystem productivity (GEP) only in the GrP. When calculating the yearly differences in phenophases and the corresponding carbon fluxes, we found that an extended GrP greatly enhanced NEE, but a prolonged ReP distinctly reduced it. The extended GrP also significantly promote GEP. Increases in growing season length appeared promoting ER, regardless of any phenophase. Additionally, the shifts in NEE appeared dependent of the variations in leaf area index (LAI).

Screening of a specific peptide binding to esophageal squamous carcinoma cells from phage displayed peptide library.

To select a specifically binding peptide for imaging detection of human esophageal squamous cell carcinoma (ESCC), a phage-displayed 12-mer peptide library was used to screen the peptide that bind to ESCC cells specifically. After four rounds of bio-panning, the phage recovery rate gradually increased, and specific phage clones were effectively enriched. The 60 randomly selected phage clones were tested using cellular enzyme-linked immunosorbent assay (ELISA), and 41 phage clones were identified as positive clones with the over 2.10 ratio of absorbance higher than other clones, IRP and PBS controls. From the sequencing results of the positive clones, 14 peptide sequences were obtained and ESCP9 consensus sequence was identified as the peptide with best affinity to ESCC cells via competitive inhibition, fluorescence microscopy, and flow cytometry. The results indicate that the peptide ESCP9 can bind to ESCC cells specifically and sensitively, and it is a potential candidate to be developed as an useful molecule to the imaging detection and targeting therapy for ESCC.

Screening and identification of a specific peptide binding to hepatocellular carcinoma cells from a phage display peptide library.

To screen and identify the novel probe markers binding hepatocellular carcinoma specifically and sensitively, a phage-displayed 12-mer peptide library was used to make biopanning with the modified protocols on HepG2 cells. After four rounds of panning, the consensus sequences were obtained, and the PC28, a phage clone with most specific and sensitive binding to HepG2 cells, was identified as the best positive clone. The peptide probe HCSP4 (sequence SLDSTHTHAPWP) was synthesized based on the sequencing result of PC28. The specificity and sensitivity of HCSP4 were primarily analyzed using immunofluorescence, flow cytometry, and other methods. The results show that HCSP4 can bind to hepatocellular carcinoma cells with satisfactory specificity and sensitivity. It may be a promising lead candidate for molecular imaging and targeted drug delivery in the diagnosis and therapy of hepatocellular carcinoma.

Mass spectrometry methodology in lipid analysis.

Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS) is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease.

Role of the Hippo pathway in autoimmune diseases.

The immune system is an important defense against diseases, and it is essential to maintain the homeostasis of the body's internal environment. Under normal physiological conditions, the steady state of the immune system should be sustained to play normal immune response and immune function. Exploring the molecular mechanism of maintaining immune homeostasis under physiological and pathological conditions will provides understanding of the pathogenesis of autoimmune diseases, infections, metabolic disorders, and tumors, as well as new ideas and molecular targets for the prevention and treatment of these diseases. Hippo signaling pathway can not only regulate immune cells such as macrophages, T cells and dendritic cells, but also interact with immune-related signaling pathways such as NF-kB signaling pathway, TGF-ß signaling pathway and Toll-like receptor signaling pathway, so as to resist the internal environment disorder caused by the invasion of exogenous pathogenic microorganisms and maintain the internal environment stability and physiological balance of the body. Hippo signaling pathway is also involved in the pathological process of immune system-related diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Hippo pathway is closely related to organ development, stem cell biology, regeneration, and tumor biology. It affects cell differentiation by participating in extracellular and intracellular physiological signal reactions, sensing cell environment, and coordinating cell reactions. This pathway is crucial in maintaining immune homeostasis. This review summarizes the mechanism of Hippo pathway in different immune cells and some autoimmune diseases and the interaction between different immune signaling pathways and Hippo signaling pathway. It aims to explore the role of Hippo in autoimmune diseases and provide theoretical and practical basis for the treatment of autoimmune diseases through Hippo signaling pathway.