Although mesenchymal stromal cells (MSCs) have demonstrated great therapeutic potential, the heterogeneity of MSCs may be responsible for the incongruent data obtained in MSC-based preclinical studies and clinical trials. Here, four mouse clonal MSC lines, termed MSC1, MSC2, MSC3, and MSC4, were isolated and extensively characterized. MSC4 cells grew most rapidly and formed colonies of the largest size, whereas MSC3 cells exhibited the slowest growth and formed only a few tiny clusters. MSC4 cells could differentiate into adipocytes, osteoblasts, and chondrocytes in vitro, and more importantly, establish hematopoietic microenvironment in vivo; whereas the other lines displayed uni-adipogenic, osteo-chondrogenic, or non-differentiation potential. All lines were positive for Sca-1, CD106, and CD44; MSC4 was also positive for CD90.2. In terms of immunosuppressive capacity, MSC2, MSC3, and MSC4 cells exerted clear inhibitory effects on lymphocyte proliferation, whereas MSC1 did not. Further investigation revealed that the NO and not the PGE2 pathway may play a role in the different immunomodulatory effects of the cell lines. To clarify the molecular basis of this heterogeneity, we employed RNA sequencing to compare the gene expression profiles of the four subtypes, revealing a relationship between gene expression and variability in subtype function. This study provides novel information about the heterogeneity of MSCs and insight into the selection of optimal cell sources for therapeutic applications.

Mesenchymal stromal cells (MSCs) have shown great potential for treating inflammatory bowel disease, which is ameliorated through paracrine cross talk between MSCs and T-cells. Members of the insulin-like growth factor binding protein (IGFBP) family have important immunomodulatory functions in MSCs, but the underlying mechanisms behind these functions have not yet been clearly elucidated. In this study, we investigate whether MSC-produced IGFBP7 is involved in immune modulation using a mouse experimental colitis model. Gene expression profiling revealed that IGFBP7 was highly expressed in MSCs. Consistent with this findings, IGFBP7 knockdown in MSCs significantly decreased their immunomodulatory properties, decreasing the antiproliferative functions of MSCs against T-cells, while also having an effect on the proinflammatory cytokine production of the T-cells. Furthermore, in the mouse experimental colitis model, MSC-derived IGFBP7 ameliorated the clinical and histopathological severity of induced colonic inflammation and also restored the injured gastrointestinal mucosal tissues. In conclusion, IGFBP7 contributes significantly to MSC-mediated immune modulation, as is shown by the ability of IGFBP7 knockdown in MSCs to restore proliferation and cytokine production in T-cells. These results suggest that IGFBP7 may act as a novel MSC-secreted immunomodulatory factor.

BACKGROUND Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein cloned from activated macrophages in human and rat allografts. AIF-1 has been identified as a modulator of inflammatory response, and recently published studies have shown its increased expression in carcinogenesis. However, there are still limited data on the potential functional role of AIF-1 in hepatocellular carcinoma (HCC). MATERIAL AND METHODS We evaluated the expression of AIF-1 in 104 cases of paired HCC and adjacent non-cancerous liver tissues using immunohistochemistry, Western blotting, and qPCR analysis, and sought to determine whether its expression was correlated with clinicopathological features. In vitro assays, including cell proliferation and migration assays, were used to study the effects of AIF-1 knockdown in L02 human hepatocyte, and Huh7 and SMMC7721 liver cancer cell lines. RESULTS Expression of AIF-1 was increased in HCC compared to adjacent normal liver tissues and was positively correlated with median tumor size (p=0.046), number of tumor deposits (p=0.009), the Barcelona Clinic Liver Cancer (BCLC) stage (p=0.004), and portal vein tumor thrombus (PVTT) (p<0.001). Huh7 and SMMC7721 human HCC cells demonstrated upregulated AIF-1 expression compared to normal hepatocytes. Small interfering RNA (siRNA)-mediated silencing of AIF-1 expression resulted in a reduction in cell proliferation and migration in human HCC cells. CONCLUSIONS These findings suggest AIF-1 may have roles as a diagnostic or prognostic biomarker and a promising therapeutic target in HCC.

The present study aimed to investigate the effect of Dickkopf-related protein 3 (DKK3) on osteogenic differentiation of rat dental follicle cells (DFCs). A PCR array analysis of Wnt pathway activation in DFCs identified genes dysregulated by mineral induction. Among them, DKK3expression levels were decreased, and further experiments were conducted to investigate its role in DFC osteogenesis. By comparing DFCs grown in normal growth and mineral‑induction media for 4 weeks, the present study confirmed that DKK3 was a potential target gene of osteogenesis through reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) and western blotting (WB). A short hairpin RNA (shRNA) was introduced into DFCs using a lentiviral vector to inhibit DKK3 expression. An alkaline phosphatase (ALP) activity assay and Alizarin Red staining were performed to observe the DKK3‑shRNA DFCs. In addition, the osteogenic differentiation of DKK3‑shRNA DFCs was analyzed by RT‑qPCR and WB. In vivo, DKK3‑shRNA DFCs seeded on hydroxyapatite/β-tricalcium phosphate (HA/TCP) scaffolds were transplanted into the subcutaneous tissue of mice with severe combined immunodeficiency, followed by hematoxylin‑eosin and Masson staining. The results confirmed that DKK3 expression was downregulated during mineral induction in rat DFCs. Lentivirus‑mediated expression of DKK3 shRNA in DFCs promoted calcified‑nodule formation, ALP activity and the expression of β‑catenin, runt‑related transcription factor 2 and osteocalcin, compared with control cells. In vivo, the implanted section presented the majority of newly formed osteoid matrices and collagen, with limited space between the HA/TCP scaffolds and matrices. In conclusion, DKK3 expression negatively regulates the osteogenic differentiation of DFCs and, conversely, downregulation of DKK3 may enhance DFC osteogenesis.

Glial scar impedes axon regeneration and functional recovery following traumatic brain injury (TBI). Although it has been shown that rapamycin (a specific inhibitor of mammalian target of rapamycin) can reduce astrocyte reactivation in the early stage of TBI, its effect on glial scar formation has not been characterized in TBI and other acute brain injury models. To test this, ICR mice received daily administration of rapamycin (0.5 or 1.5 mg/kg, i.p.) beginning at 1 h after cryogenic TBI (cTBI). The results showed that at 3 d post-injury, 1.5 mg/kg rapamycin increased cTBI-induced motor functional deficits and infarct size, and attenuated astrocyte reactivation in the ipsilateral cortex, while 0.5 mg/kg rapamycin did not worsen brain damage and only slightly attenuated astrocyte reactivation. Furthermore, at 7 and 14 d after cTBI, 0.5 mg/kg rapamycin group showed a better motor functional performance than cTBI group. At 14 d post-injury, 0.5 mg/kg rapamycin significantly reduced the area and thickness of glial scar and chondroitin sulfate proteoglycan expression, accompanied by decreased expression of p-S6 and enhanced expression of growth associated protein 43 (an axon regeneration marker) in the region of glial scar. Our data suggest that long-term treatment with rapamycin can inhibit glial scar formation after cTBI, which may be involved in the mechanisms of increased axon regeneration and improved neurological functional recovery, and low-dose rapamycin may be more beneficial for such a therapy.

Although it has been previously documented that a hypoxic environment can promote glycolysis and the malignant progression of oral squamous cell carcinoma (OSCC) cells, the specific underlying mechanism remains unclear. Phosphoglycerate kinase 1 (PGK1) has been previously reported to serve an important role in tumor metabolism. The aim of the present study was to investigate the effects of hypoxia and PGK1 on glycolysis, stem cell‑like properties and epithelial‑mesenchymal transition (EMT) in OSCC cells. Cell Counting Kit‑8 assays were performed to examine tumor cell viability under hypoxic conditions. Sphere formation, immunohistochemistry, western blotting, Transwell assays and mouse xenograft studies were performed to assess the biological effects of PGK1. Under hypoxic conditions, phosphoglycerate PGK1 expression was found to be upregulated, which resulted in the potentiation of stem cell‑like properties and enhancement of EMT. However, PGK1 knockdown reversed hypoxia‑mediated glycolysis, stem cell‑like properties, EMT in addition to inhibiting OSCC cell invasion and migration. PGK1 knockdown also inhibited tumour growth, whilst the overexpression of PGK1 was demonstrated to promote tumour growth in mouse xenograft models in vivo. Downstream, activation of the AKT signalling pathway reversed the series of changes induced by PGK1 knockdown. PGK1 expression was found to be upregulated in human OSCC tissues, which was associated with the pathological differentiation of tumours and lymph node metastasis. To conclude, results from the present study demonstrate that hypoxia can increase PGK1 expression, resulting in the promotion of glycolysis, enhancing stem cell‑like properties and EMT by activating AKT signalling in OSCC.

Most hepatocellular carcinoma (HCC) patients' liver function indexes are abnormal. We aimed to investigate the relationship between (alkaline phosphatase + gamma-glutamyl transpeptidase)/lymphocyte ratio (AGLR) and the progression as well as the prognosis of HCC.

As one of the most common malignancies worldwide, Hepatocellular carcinoma (HCC) has been treated by Sorafenib, which is the first approved target drug by FDA for advanced HCC. However, drug resistance is one of the obstacles to its application. As a typical characteristic of most solid tumors, hypoxia has become a key cause of resistance to chemotherapy and radiotherapy. It is important to elucidate the underlying mechanisms of Sorafenib resistance under hypoxia. In this study, the morphological changes of hepatocellular carcinoma cells were observed by Live Cell Imaging System and Transmission Electron Microscope; Sorafenib was found to induce necroptosis in liver cancer. Under hypoxia, the distribution of necroptosis related proteins was changed, which contributed to Sorafenib resistance. HSP90α binds with the necrosome complex and promotes chaperone-mediated autophagy (CMA) degradation, which leads necroptosis blocking and results in Sorafenib resistance. The patient-derived tumor xenograft (PDX) model has been established to investigate the potential therapeutic strategies to overcome Sorafenib resistance. 17-AAG inhibited HSP90α and presented obvious reversal effects of Sorafenib resistance in vivo and in vitro. All the results emphasized that HSP90α plays a critical role in Sorafenib resistance under hypoxia and 17-AAG combined with Sorafenib is a promising therapy for hepatocellular carcinoma.

Crohn's disease (CD) is a chronic inflammatory bowel disease that is difficult to treat. However, previous preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach, whereas the exact underlying molecular mechanisms of MSCs in treating CD remain unclear. Furthermore, the heterogeneity of MSCs, as well as the in vivo microenvironments may influence the therapeutic efficacy. In our previous study, we found that a subpopulation of mouse MSCs with a high expression of matrix Gla protein (MGP), one of the members of vitamin K-dependent protein family, possessed better immunoregulatory properties. Therefore, in this study we investigate whether the abundant MSCs-derived MGP participate in the therapeutic mechanisms for MSCs treating CD. Obvious suppression of cell proliferation and cytokine production in T cells were observed in vitro through MSCs-derived MGP. Moreover, MGP alleviated the clinical and histopathological severity of colonic inflammation in mouse experimental colitis models to a remarkable degree. Our results indicate that MGP might be a novel important mediator of MSCs-mediated immunomodulation in treating CD.

Transcriptional regulators that integrate cellular and environmental signals to control cell division are well known in bacteria and eukaryotes, but their existence is poorly understood in archaea. We identified a conserved gene (cdrS) that encodes a small protein and is highly transcribed in the model archaeon Haloferax volcanii. The cdrS gene could not be deleted, but CRISPR interference (CRISPRi)-mediated repression of the cdrS gene caused slow growth and cell division defects and changed the expression of multiple genes and their products associated with cell division, protein degradation, and metabolism. Consistent with this complex regulatory network, overexpression of cdrS inhibited cell division, whereas overexpression of the operon encoding both CdrS and a tubulin-like cell division protein (FtsZ2) stimulated division. Chromatin immunoprecipitation-DNA sequencing (ChIP-Seq) identified 18 DNA-binding sites of the CdrS protein, including one upstream of the promoter for a cell division gene, ftsZ1, and another upstream of the essential gene dacZ, encoding diadenylate cyclase involved in c-di-AMP signaling, which is implicated in the regulation of cell division. These findings suggest that CdrS is a transcription factor that plays a central role in a regulatory network coordinating metabolism and cell division. IMPORTANCE Cell division is a central mechanism of life and is essential for growth and development. Members of the Bacteria and Eukarya have different mechanisms for cell division, which have been studied in detail. In contrast, cell division in members of the Archaea is still understudied, and its regulation is poorly understood. Interestingly, different cell division machineries appear in members of the Archaea, with the Euryarchaeota using a cell division apparatus based on the tubulin-like cytoskeletal protein FtsZ, as in bacteria. Here, we identify the small protein CdrS as essential for survival and a central regulator of cell division in the euryarchaeon Haloferax volcanii. CdrS also appears to coordinate other cellular pathways, including synthesis of signaling molecules and protein degradation. Our results show that CdrS plays a sophisticated role in cell division, including regulation of numerous associated genes. These findings are expected to initiate investigations into conditional regulation of division in archaea.

Pulmonary fibrosis (PF) is a growing clinical problem with limited therapeutic options. Human umbilical cord mesenchymal stromal cell (hucMSC) therapy is being investigated in clinical trials for the treatment of PF patients. However, little is known about the underlying molecular and cellular mechanisms of hucMSC therapy on PF. In this study, the molecular and cellular behavior of hucMSC was investigated in a bleomycin-induced mouse PF model.

Postpartum depression (PPD) is a prevalent mental health problem with serious adverse consequences for affected women and their infants. Clinical trials have found that telehealth interventions for women with PPD result in increased accessibility and improved treatment effectiveness. However, no comprehensive synthesis of evidence from clinical trials by systematic review has been conducted.

Mesenchymal stromal cells (MSCs) show potential for treating preclinical models of newborn bronchopulmonary dysplasia (BPD), but studies of their therapeutic effectiveness have had mixed results, in part due to the use of different media supplements for MSCs expansion in vitro. The current study sought to identify an optimal culture supplement of umbilical cord-derived MSCs (UC-MSCs) for BPD therapy. In this study, we found that UC-MSCs cultured with human platelet lysate (hPL-UCMSCs) were maintained a small size from Passage 1 (P1) to P10, while UC-MSCs cultured with fetal bovine serum (FBS-UCMSCs) became wide and flat. Furthermore, hPL was associated with lower levels of senescence in UC-MSCs during in vitro expansion compared with FBS, as indicated by the results of β-galactosidase staining and measures of senescence-related genes (CDKN2A, CDKN1A, and mTOR). In addition, hPL enhanced the proliferation and cell viability of the UC-MSCs and reduced their doubling time in vitro. Compared with FBS-UCMSCs, hPL-UCMSCs have a greater potential to differentiate into osteocytes and chondrocytes. Moreover, using hPL resulted in greater expression of Nestin and specific paracrine factors (VEGF, TGF-β1, FGF2, IL-8, and IL-6) in UC-MSCs compared to using FBS. Critically, we also found that hPL-UCMSCs are more effective than FBS-UCMSCs for the treatment of BPD in a rat model, with hPL leading to improvements in survival rate, lung architecture and fibrosis, and lung capillary density. Finally, qPCR of rat lung mRNA demonstrated that hPL-UCMSCs had lower expression levels of inflammatory factors (TNF-α and IL-1β) and a key chemokine (MCP-1) at postnatal day 10, and there was significant reduction of CD68+ macrophages in lung tissue after hPL-UCMSCs transplantation. Altogether, our findings suggest that hPL is an optimal culture supplement for UC-MSCs expansion in vitro, and that hPL-UCMSCs promote lung repair in rat BPD disease.

SPC24 is an important component of the nuclear division cycle 80 (Ndc80) kinetochore complex, which plays an essential role in the coupling of kinetochore to spindle microtubules (MTs) and the accurate segregation of chromosomes during mitosis. However, the functional role of SPC24 in hepatocellular carcinoma (HCC) remains unknown. Here, we detected the expression of SPC24 in HCC and analyzed its association with clinicopathologic features and prognosis of HCC patients. The expression of SPC24 mRNA was investigated in 212 cases of paired HCC and adjacent liver tissues by quantitative real-time PCR (qRT-PCR) and in the tissues of 20 HCC patients by semi-quantitative RT-PCR. Additionally, the expression of SPC24 protein was detected in 69 cases of HCC by immunohistochemistry (IHC) or in 2 cases of HCC tissues by Western-blotting. Furthermore, small interfering RNA (siRNA)-mediated silencing of SPC24 was employed in SMMC7721 and HepG2 human HCC cells to investigate cell proliferation, invasion and apoptosis. Survival curves were plotted using the Kaplan-Meier method, and differences in survival probability were obtained using the log-rank test. Independent predictors associated with disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox proportional-hazards regression model. In this study, we showed that SPC24 was noticeably increased in HCC tissues compared to normal adjacent noncancerous tissues, at both mRNA and protein levels. High expression of SPC24 was significantly correlated with alpha-fetoprotein (AFP) (p = 0.044), median size (p = 0.030), tumor number (p = 0.019), and Barcelona-Clinic Liver Cancer (BCLC) stage (p = 0.015). Kaplan-Meier analysis showed that the DFS and OS of high SPC24 expression group was significantly shorter than that of low SPC24 expression group (p < 0.001; p = 0.001; respectively). The prognostic impact of SPC24 was further confirmed by stratified survival analysis. Importantly, multivariate analysis identified SPC24 upregualtion (p = 0.001), PVTT (p = 0.007), size of tumor > 5 cm (p < 0.001) as independent risk factors of DFS after resection, and SPC24 upregualtion (p < 0.001), PVTT (p = 0.029), size of tumor > 5 cm (p = 0.002), recurrence (p < 0.001) as independent prognostic factors for the OS of HCC patients. Additionally, siRNA-mediated silencing of SPC24 dramatically suppressed cell growth, adhesion, invasion and increased apoptosis in HCC cells. In conclusion, these results showed for the first time that SPC24 expression was significantly up-regulated in HCC, which may act as a novel prognostic biomarker for patients suffering from this deadly disease. Additionally, silence of SPC24 inhibiting HCC cell growth indicated that SPC24 may be a promising molecular target for HCC therapy.

Bone-derived mesenchymal stem cell (BMSC) transplantation has been reported to be effective for the treatment of ischemic heart disease, but whether BMSCs are the optimal cell type remains under debate. Increasing numbers of studies have shown that Nestin, an intermediate filament protein, is a potential marker for MSCs, which raises the question of whether Nestin+ cells in BMSCs may play a more crucial role in myocardial repair.

Intestinal epithelial cell (IEC) cycle arrest has recently been found to be involved in the pathogenesis of Crohn's disease (CD). However, the mechanism underlying the regulation of this form of cell cycle arrest, remains unclear. Here, we investigated the roles that advanced oxidation protein products (AOPPs) may play in regulating IEC cycle arrest. Plasma AOPPs levels and IEC cycle distributions were evaluated in 12 patients with CD. Molecular changes in various cyclins, cyclin-dependent kinases (CDKs), and other regulatory molecules were examined in cultured immortalized rat intestinal epithelial (IEC-6) cells after treatment with AOPPs. The in vivo effects exerted by AOPPs were evaluated using a normal C57BL/6 mouse model with an acute AOPPs challenge. Interestingly, plasma AOPPs levels were elevated in active CD patients and correlated with IEC G1 phase arrest. In addition, IEC treatment with AOPPs markedly reduced the expression of cyclin E and CDK2, thus sensitizing epithelial cells to cell cycle arrest both in vitro and in vivo. Importantly, we found that AOPPs induced IEC G1 phase arrest by modulating two membrane receptors, RAGE and CD36. Furthermore, phosphorylation of c-jun N-terminal kinase (JNK) and the expression of p27kip1 in AOPPs-treated cells were subsequently increased and thus affected cell cycle progression. Our findings reveal that AOPPs influence IEC cycle progression by reducing cyclin E and CDK2 expression through RAGE/CD36-depedent JNK/p27kip1 signaling. Consequently, AOPPs may represent a potential therapeutic molecule. Targeting AOPPs may offer a novel approach to managing CD.

Aerobic glycolysis is the main pathway for energy metabolism in cancer cells. It provides energy and biosynthetic substances for tumor progression and metastasis by increasing lactate production. Lactate dehydrogenase A (LDHA) promotes glycolysis process by catalyzing the conversion of pyruvate to lactate. Despite LDHA exhibiting carcinogenesis in various cancers, its role in oral squamous cell carcinoma (OSCC) remains unclear. This study demonstrated that LDHA was over-expressed in both OSCC tissues and cell lines, and was significantly associated with lower overall survival rates in patients with OSCC. Using weighted gene correlation network analysis and gene set enrichment analysis for the gene expression data of patients with OSCC (obtained from The Cancer Genome Atlas database), a close association was identified between epithelial-mesenchymal transition (EMT) and LDHA in promoting OSCC progression. The knockdown of LDHA suppressed EMT, cell proliferation, and migration and invasion of OSCC cells in vitro. Moreover, the silencing of LDHA inhibited tumor growth in vivo. Oxamate, as a competitive LDHA inhibitor, was also suppressed diverse malignant biocharacteristics of OSCC cells. Our findings reveal that LDHA acts as an oncogene to promote malignant progression of OSCC by facilitating glycolysis and EMT, and LDHA may be a potential anticancer therapeutic target.

Previous studies implicated ATX/LPA axis as a potential driver of tumorigenesis and progression in pancreatic cancer. This study aimed to determine the existence of the autocrine pathway of ATX/LPA action in pancreatic cancer cells, and to elucidate its influence on focal adhesion kinase (FAK) activation, cellular proliferation, apoptosis, and migration. Firstly, we identified the lysophosphatidic acid (LPA) concentrations in cultured cell supernatant by ELISA and observed the effect of the autotaxin (ATX)-specific inhibitor S32826 on LPA concentrations. We found the existence of a certain concentration of LPA in cellular supernatant, which was significantly decreased by S32826 in a dose- and time-dependent manner. A maximum response was observed at 50 μM for 72 h. Secondly, the effect of S32826 on the protein expression and intracellular sublocalization of total FAK and phosphorylated FAK (pY397 FAK) was determined by Western blot and immunofluorescence staining. It was found that the expression of total FAK and pY397 FAK and their distribution along the cell membrane where adhesion structures are located were significantly decreased by S32826. Finally, we observed the influence of S32826 on cell proliferation, apoptosis, and migration by CCK-8 assay, flow cytometric analysis, and transwell migration assay. Results showed that cell viability and migration were significantly declined, and the proportions of apoptotic cells were significantly increased by S32826. This study verified the existence of autocrine regulation of LPA secretion via producing ATX by pancreatic cancer cells in vitro and the important role of LPA/ATX axis on FAK activation, cell proliferation, apoptosis, and motility.

Sijunzi, Lizhong, and Fuzilizhong decoction were traditional Chinese classic formulations, which are widely used in clinical treatment, and the underlying mechanism is unclear. In this study, we aim to investigate the molecular mechanisms underlying the protective effects of Sijunzi, Lizhong, and Fuzilizhong on nonalcoholic fatty liver disease (NAFLD).

Endometriosis is the most major cause of chronic pelvic pain in women of reproductive age. Moreover, the involvement of histone deacetylase 2 (HDAC2) has been identified in endometriosis. However, the specific mechanism of HDAC2 remains to be further elusive. Therefore, this study was designed to explore the mechanism of HDAC2 orchestrating hepatocyte nuclear factor 4α/AT-rich interactive domain 1A (HNF4A/ARID1A) axis in endometriosis. Endometriosis cell line hEM15A and clinical endometriosis tissues were obtained, followed by gain- and loss-of-function assays in hEM15A cells. HDAC2, HNF4A and ARID1A expression was detected by immunohistochemistry and Western blot analysis. Cell viability was determined by Cell Counting Kit-8 Assay, invasion by Transwell assay and apoptosis by flow cytometry. HDAC2 enrichment in HNF4A promoter region and HNF4A enrichment in ARID1A promoter region was detected through chromatin immunoprecipitation. Mouse models of endometriosis were established, followed by immunohistochemistry of Ki-67 expression and TUNEL staining of apoptosis in ectopic tissues. HDAC2 was upregulated but HNF4A and ARID1A were downregulated in endometriosis tissues. HDAC2 inhibited HNF4A expression by deacetylation, and HNF4A was enriched in ARID1A promoter region to activate ARID1A. Silencing HDAC2 or overexpressing HNF4A or ARID1A diminished the viability and invasion and augmented the apoptosis of hEM15A cells. HDAC2 silencing reduced the area and weight of endometriosis tissues, suppressed endometriosis cell proliferation and accelerated endometriosis cell apoptosis. The inhibitory action of silencing HDAC2 via HNF4A/ARID1A axis was reproduced in mouse models. Collectively, HDAC2 silencing might upregulate HNF4A via repression of deacetylation to activate ARID1A, thus preventing the occurrence of endometriosis.