Cell Animal Models Research Articles

Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression

Salivary gland cancer (SGC) represents the most common malignancy in the head and neck region, and often metastasizes to the lungs. The helix–loop–helix ID1 protein has been shown to control metastatic progression in many types of cancers. Using two different approaches to target the expression of ID1 (genetic knockdown and progesterone receptor introduction combined with progesterone treatment), we previously determined that the aggressiveness of salivary gland tumor ACCM cells in culture was suppressed. Here, using the same approaches to target ID1 expression, we investigated the ability of ACCM cells to generate lung metastatic foci in nude mice. Moreover, since both approaches would be challenging for applications in humans, we added a third approach, i.e., treatment of mice with a non-toxic cannabinoid compound known to down-regulate ID1 gene expression. All approaches aimed at targeting the pro-metastatic ID1 gene led to a significant reduction in the formation of lung metastatic foci. Therefore, targeting a key transcriptional regulator using different means results in the same reduction of the metastatic spread of SGC cells in animal models, suggesting a novel approach for the treatment of patients with aggressive SGC.

Therapeutic Potential of Human-Derived Endothelial Colony-Forming Cells in Animal Models.

Tissue regeneration requires proper vascularization. In vivo studies identified that the endothelial colony-forming cells (ECFCs), a subtype of endothelial progenitor cells that can be isolated from umbilical cord or peripheral blood, represent a promising cell source for therapeutic neovascularization. ECFCs not only are able to initiate and facilitate neovascularization in diseased tissue but also can, by acting in a paracrine manner, contribute to the creation of favorable conditions for efficient and appropriate differentiation of tissue-resident stem or progenitor cells. This review outlines the progress in the field of in vivo regenerative and tissue engineering studies and surveys why, when, and how ECFCs can be used for tissue regeneration. Reviewed literature that regard human-derived ECFCs in xenogeneic animal models implicates that ECFCs should be considered as an endothelial cell source of preference for induction of neovascularization. Their neovascularization and regenerative potential is augmented in combination with other types of stem or progenitor cells. Biocompatible scaffolds prevascularized with ECFCs interconnect faster and better with the host vasculature. The physical incorporation of ECFCs in newly formed blood vessels grants prolonged release of trophic factors of interest, which also makes ECFCs an interesting cell source candidate for gene therapy and delivery of bioactive compounds in targeted area. ECFCs possess all biological features to be considered as a cell source of preference for tissue engineering and repair of blood supply. Investigation of regenerative potential of ECFCs in autologous settings in large animal models before clinical application is the next step to clearly outline the most efficient strategy for using ECFCs as treatment.

Auraptene induces oligodendrocyte lineage precursor cells in a cuprizone-induced animal model of demyelination

We investigated the effects of auraptene on mouse oligodendroglial cell lineage in an animal model of demyelination induced by cuprizone. Auraptene, a citrus coumarin, was intraperitoneally administered to mice fed the demyelinating agent cuprizone. Immunohistochemical analysis of the corpus callosum and/or Western blotting analysis of brain extracts revealed that cuprizone reduced immunoreactivity for myelin-basic protein, a marker of myelin, whereas it increased immunoreactivity to platelet derived-growth factor receptor-α, a marker of oligodendrocyte precursor cells. Administration of auraptene enhanced the immunoreactivity to oligodendrocyte transcription factor 2, a marker of oligodendrocyte precursor cells and oligodendrocyte lineage precursor cells, but had no effect on immunoreactivity to myelin-basic protein or platelet-derived growth factor receptor-α. These findings suggest that auraptene promotes the production of oligodendrocyte lineage precursor cells in an animal model of demyelination and may be useful for individuals with demyelinating diseases.

Caveolin- and clathrin-independent entry of BKPyV into primary human proximal tubule epithelial cells

BK polyomavirus (BKPyV) is a human pathogen that causes polyomavirus-associated nephropathy and hemorrhagic cystitis in transplant patients. Gangliosides and caveolin proteins have previously been reported to be required for BKPyV infection in animal cell models. Recent studies from our lab and others, however, have indicated that the identity of the cells used for infection studies can greatly influence the behavior of the virus. We therefore wished to re-examine BKPyV entry in a physiologically relevant primary cell culture model, human renal proximal tubule epithelial cells. Using siRNA knockdowns, we interfered with expression of UDP-glucose ceramide glucosyltransferase (UGCG), and the endocytic vesicle coat proteins caveolin 1, caveolin 2, and clathrin heavy chain. The results demonstrate that while BKPyV does require gangliosides for efficient infection, it can enter its natural host cells via a caveolin- and clathrin-independent pathway. The results emphasize the importance of studying viruses in a relevant cell culture model.

Artificial vesicles as an animal cell model for the study of biological application of non-thermal plasma

Artificial cell-like model systems can provide information which is hard to obtain with real biological cells. Giant unilamellar vesicles (GUV) containing intra-membrane DNA or OH radical-binding molecules are used to visualize the cytolytic activity of OH radicals. Changes in the GUV membrane are observed by microscopy or flow cytometry as performed for animal cells after non-thermal plasma treatment. The experimental data shows that OH radicals can be detected inside the membrane, although the biological effects are not as significant as for H2O2. This artificial model system can provide a systemic means to elucidate the complex interactions between biological materials and non-thermal plasma.

The Parkinson's-disease-associated receptor GPR37 undergoes metalloproteinase-mediated N-terminal cleavage and ectodomain shedding.

The G-protein-coupled receptor 37 ( GPR37) has been implicated in the juvenile form of Parkinson's disease, in dopamine signalling and in the survival of dopaminergic cells in animal models. The structure and function of the receptor, however, have remained enigmatic. Here, we demonstrate that although GPR37 matures and is exported from the endoplasmic reticulum in a normal manner upon heterologous expression in HEK293 and SH-SY5Y cells, its long extracellular N-terminus is subject to metalloproteinase-mediated limited proteolysis between E167 and Q168. The proteolytic processing is a rapid and efficient process that occurs constitutively. Moreover, the GPR37 ectodomain is released from cells by shedding, a phenomenon rarely described for GPCRs. Immunofluorescence microscopy further established that although full-length receptors are present in the secretory pathway until the trans-Golgi network, GPR37 is expressed at the cell surface predominantly in the N-terminally truncated form. This notion was verified by flow cytometry and cell surface biotinylation assays. These new findings on the GPR37 N-terminal limited proteolysis may help us to understand the role of this GPCR in the pathophysiology of Parkinson's disease and in neuronal function in general.

Induced Pluripotent Stem Cells: Development in the Ophthalmologic Field

Human induced pluripotent stem cells (iPSCs) are a type of stem cells that can be derived from human somatic cells by introducing certain transcription factors. Induced pluripotent stem cells can divide indefinitely and are able to differentiate into every cell type, which make them viable for transplantation and individual disease modeling. Recently, various ocular cells, including corneal epithelial-like cells, retinal pigment epithelium (RPE) cells displaying functions similar to native RPE, photoreceptors, and retinal ganglion cells, have all been successfully derived from iPSCs. Transplantation of these cells in animal models showed great promise for reversing blindness, and the first clinical trial on humans started in 2013. Despite these promising results, more research is in demand for preventing inadvertent tumor growth, developing precise functionality of the cells, and promoting integration into the host tissue.

CD44 promotes chemoresistance in T-ALL by increased drug efflux

T-Cell acute lymphoblastic leukemia is considered a largely curable disease in children; however, adult patients and children with refractory or relapsed disease have consistently poor outcomes. On the basis of our prior work highlighting CD44 as a marker of leukemia-initiating cells in animal models and because cancer stem cells are postulated to possess intrinsic resistance to conventional chemotherapy, we examined whether CD44 itself might play a role in mediating chemoresistance. We report here that in both genetically defined mouse models and human cell lines, CD44 expression is associated with chemoresistance, and that this effect is mediated in part through enhanced drug efflux. Interestingly, we also observed increased CD44 expression in residual blasts following standard induction chemotherapy, as compared with blasts from matched, pretherapy samples in a subset of pediatric patients undergoing minimal residual disease monitoring as part of a clinical trial. These findings support a functional role for CD44 in promoting chemotherapy resistance and suggest that targeting it directly or its relevant effector pathways may improve clinical responses in T-cell acute lymphoblastic leukemia.

Gene Expression Profiling for Molecular Features of Response in a Phase I Trial of Alisertib Plus Romidepsin for Relapsed/Refractory Aggressive B- and T-Cell Lymphomas

Background: The histone deacetylase inhibitor (HDACi) romidepsin (Coiffier 2010) and other HDACi such as belinostat (O'Connor 2015) are management options for relapsed peripheral T-cell lymphoma (PTCL), and HDACi have also shown benefit for B-cell lymphomas (Younes 2012). The aurora A kinase (AURKA) inhibitor alisertib has shown promising results in aggressive lymphomas including Burkitt lymphoma (BL), diffuse large B cell lymphoma (DLBCL), and PTCL (Friedberg 2011, Barr 2014), and a registration trial in PTCL has recently completed enrollment. Given preclinical evidence for synergy when combining an AURKA inhibitor plus an HDACi (Zullo 2015, Muscal 2011, Kretzner 2008), we initiated a Phase I trial (NCT01897012, supported by CTEP-NCI) combining alisertib plus romidepsin in patients with multiple lymphoma subtypes.Methods: 12 patients have been enrolled to date, 3 at each of 4 escalation dose levels with patients treated with alisertib on days 1 to 7 and romidepsin on days 1 to 8 of 21 day cycles. Of the eligible histologies there was 1 patient with BL, 3 with DLBCL and FISH positive for translocations of MYC and BCL2 (double-hit lymphoma, DHL), 4 with DLBCL with other unfavorable features (FISH-positive for c-myc alone; 90% Ki-67 positive; high protein staining for MYC and BCL2, but not FISH-positive; and transformed from follicular lymphoma), 3 with PTCL, and 1 with composite PTCL and DLBCL (Fanale 2014). Tumor core biopsies were performed at baseline and at the end of 1 cycle of therapy, part of which was collected in RNAlater for gene expression profiling (GEP) using Illumina HT12v4.0 arrays. Whole peripheral blood was also collected at these and other time points in PAXgene tubes for future GEP.Results: Dose escalation and safety data have been previously presented (Fanale 2014). Responses to date are CR (PTCL, dose level 1), SD (PTCL, dose level 3, composite PTCL/DLBCL, dose level 4), PD (3 DHL, 1 HG DLBCL, 1 DLBCL with c-Myc, 1 PTCL). 4 of the patients with PD have died from continued refractory disease and 1 has been transitioned to hospice. The CR patient received 7 prior lines of treatment and had a duration of remission of 10 month. The PTCL patient with SD underwent an allogeneic stem cell transplant (SCT) but developed further PD 5 months after completion of SCT.Technically-satisfactory GEP results were obtained for 9 pairs of baseline (pre-Rx) and post-cycle 1 (post-Rx) tumor biopsies. Hierarchical clustering of highly-variant genes across all samples, including additional samples from 2 patients (pre-Rx only), showed appropriate grouping of samples according to B- or T-cell lineage. For all but one sample pair, pre-Rx and post-Rx samples from the same patient clustered as nearest neighbors, indicating that treatment had less effect on GEP data than did patient origin, and that "subtraction" (comparing post-Rx to pre-Rx samples) would be necessary for comparing treatment effects. To identify treatment-induced GEP changes associated with response to alisertib plus romidepsin, log2-transformed and subtracted data for the lone patient (with PTCL) who reached CR were compared to those for the other 8 pairs. There were 160 gene probes that were upregulated by log2 >=1.5 in the lone responder, but by >=0.75 in 2 or fewer of the other patients; similarly, 163 probes were downregulated by log2 <=-1.5 in the lone responder, but by <=-0.75 in 2 or fewer of the other patients. The hypergeometric distribution test showed that upregulated genes were enriched with high significance for genes involved in cell cycle progression, including both AURKA and AURKB (more than 4-fold); interpretation is uncertain, but could indicate compensation for functional inhibition of aurora kinases. Individual, uniquely-upregulated genes suggested induction of an anti-tumor immune response: >5-fold induction of TMSB15A, repressed by TGF-beta, and BATF3, essential for CD8a+ dendritic cells in animal models of anti-tumor immune response; and >3-fold induction of TNFRSF18 (GITR), upregulated by T-cell activation.Conclusions: Based on toxicity and response profile thus far, an amendment is under review to modify dosing schema for alisertib and romidepsin, and once the MTD is reached a potential cohort expansion for PTCL patients is planned. GEP changes suggest that induction of an antitumor response may underlie clinical responses, and will be investigated further by other studies of tumor biopsies and whole-blood GEP. DisclosuresNo relevant conflicts of interest to declare.

Neural and mesenchymal stem cells in animal models of Huntington's disease: past experiences and future challenges.

Huntington’s disease (HD) is an inherited disease that causes progressive nerve cell degeneration. It is triggered by a mutation in the HTT gene that strongly influences functional abilities and usually results in movement, cognitive and psychiatric disorders. HD is incurable, although treatments are available to help manage symptoms and to delay the physical, mental and behavioral declines associated with the condition. Stem cells are the essential building blocks of life, and play a crucial role in the genesis and development of all higher organisms. Ablative surgical procedures and fetal tissue cell transplantation, which are still experimental, demonstrate low rates of recovery in HD patients. Due to neuronal cell death caused by accumulation of the mutated huntingtin (mHTT) protein, it is unlikely that such brain damage can be treated solely by drug-based therapies. Stem cell-based therapies are important in order to reconstruct damaged brain areas in HD patients. These therapies have a dual role: stem cell paracrine action, stimulating local cell survival, and brain tissue regeneration through the production of new neurons from the intrinsic and likely from donor stem cells. This review summarizes current knowledge on neural stem/progenitor cell and mesenchymal stem cell transplantation, which has been carried out in several animal models of HD, discussing cell distribution, survival and differentiation after transplantation, as well as functional recovery and anatomic improvements associated with these approaches. We also discuss the usefulness of this information for future preclinical and clinical studies in HD.

TrkB Signaling in Retinal Glia Stimulates Neuroprotection after Optic Nerve Injury

Brain-derived neurotrophic factor (BDNF) regulates neural cell survival mainly by activating TrkB receptors. Several lines of evidence support a key role for BDNF-TrkB signaling in survival of adult retinal ganglion cells in animal models of optic nerve injury (ONI), but the neuroprotective effect of exogenous BDNF is transient. Glial cells have recently attracted considerable attention as mediators of neural cell survival, and TrkB expression in retinal glia suggests its role in neuroprotection. To elucidate this point directly, we examined the effect of ONI on TrkB(flox/flox):glial fibrillary acidic protein (GFAP)-Cre+ (TrkB(GFAP)) knockout (KO) mice, in which TrkB is deleted in retinal glial cells. ONI markedly increased mRNA expression levels of basic fibroblast growth factor (bFGF) in wild-type (WT) mice but not in TrkB(GFAP) KO mice. Immunohistochemical analysis at 7 days after ONI (d7) revealed bFGF up-regulation mainly occurred in Müller glia. ONI-induced retinal ganglion cell loss in WT mice was consistently mild compared with TrkB(GFAP) KO mice at d7. On the other hand, ONI severely decreased TrkB expression in both WT and TrkB(GFAP) KO mice after d7, and the severity of retinal degeneration was comparable with TrkB(GFAP) KO mice at d14. Our data provide direct evidence that glial TrkB signaling plays an important role in the early stage of neural protection after traumatic injury.

TGR5 is essential for bile acid-dependent cholangiocyte proliferation in vivo and in vitro

ObjectiveCholestatic liver diseases in humans as well as bile acid (BA)-feeding and common bile duct ligation (CBDL) in rodents trigger hyperplasia of cholangiocytes within the portal fields. Furthermore, elevation of...

RhoGDI deficiency induces constitutive activation of Rho GTPases and COX-2 pathways in association with breast cancer progression.

Rho GDP Dissociation Inhibitor (RhoGDI) is a key regulator of Rho GTPases. Here we report that loss of RhoGDI significantly accelerated xenograft tumor growth of MDA-MB-231 cells in animal models. At the molecular level, RhoGDI depletion resulted in constitutive activation of Rho GTPases, including RhoA, Cdc42, and Rac1. This was accompanied by Rho GTPase translocation from the cytosol to membrane compartments. Notably, COX-2 protein levels, mRNA expression, and biological activity were markedly increased in RhoGDI-deficient cells. The upregulated expression of COX-2 was directly associated with increased Rho GTPase activity. Further, we assessed the expression level of RhoGDI protein in breast tumor specimens (n = 165) by immunohistochemistry. We found that RhoGDI expression is higher in the early stages of breast cancer followed by a significant decrease in malignant tumors and metastatic lesions (p < 0.01). These data suggest that downregulation of RhoGDI could be a critical mechanism of breast tumor development, which may involve the hyperactivation of Rho GTPases and upregulation of COX-2 activity. Additional studies are warranted to evaluate the therapeutic potential of inhibiting Rho GTPases and COX-2 for treating breast cancers.

Stroke Therapy: the Potential of Amniotic Fluid-Derived Stem Cells

This article describes the clinical potential of cells harvested from human amniotic fluid in regenerative medicine, especially for stroke therapy. Amniotic fluid has been investigated as a new cell source for mesenchymal stem cells in the development of future cell-based transplantation. In this paper we highlight the characteristics of amniotic fluid-derived cells, as well as the functional benefits of these cells in animal models of stroke, altogether supporting the utility of amniotic fluid as stem cell source for cell therapy in stroke. The human amnion and amniotic fluid have attracted attention in recent years as possible reserves of stem cells that may have clinical application in the field of regenerative medicine. Several studies have examined the differentiation potential of cells derived from these two sources and concluded that they display high plasticity [1]. Currently, most studies have focused on cells derived from the amnion and revealed that amnion cell transplantation promotes re-epithelialization, modulates differentiation and angiogenesis and decreases inflammation, apoptosis and fibrosis [1–4]. This paper seeks to highlight what is currently known of the lesser studied, amniotic fluid-derived stem cells (AFSCs), and to acknowledge their potential clinical application for stroke therapy. Additionally, we will compare the advantages and disadvantages of amniotic fluid versus amnion membrane stem cells.

Thymoquinone Anticancer Discovery: Possible Mechanisms.

Medicinal plants are known for their many advantages, including the ability to treat diseases such as cancer. Nigella sativa and its active constituent thymoquinone (TQ) have long been used in traditional medicine for treating various conditions related to the respiratory and gastrointestinal systems as well as breast, colorectal, gastric, hepatic, pancreatic cancers and leukemia. TQ has been documented to possess chemo-preventive and chemotherapeutic antitumor effects. Studies reported that TQ inhibits the growth of cancer cells in animal models and culture tumors. This review summarizes the in vitro and in vivo possible mechanisms of TQ anticancer effect.

Human Progenitor Cell Quantification After Xenotransplantation in Rat and Mouse Models by a Sensitive qPCR Assay.

Xenotransplantation of human cells in animal models is an essential tool for evaluation of safety and efficacy of cell-based products for therapeutic use. Sensitive and reproducible methods are needed to detect and quantify human cells engrafted into the host tissue either in the targeted organ or in undesired locations. We developed a robust quantitative polymerase chain reaction (qPCR) assay based on amplification of human AluYb8 repeats, to assess the number of human cells present in rat or mouse tissues after transplantation. Standard curves of mixed human/rodent DNA and mixed human/rodent cells have been performed to determine the limit of detection and linear range of the assay. Standard curves from DNA mixing differed significantly from standard curves from cell mixing. We show here that the AluYb8 qPCR assay is highly reproducible and is able to quantify human cells in a rodent cell matrix over a large linear range that extends from 50% to 0.01% human cells. Short-term in vivo studies showed that human cells could be quantified in mouse liver up to 7 days after intrasplenic transplantation and in rat liver 4 h after intrahepatic transplantation.

Sur1-Trpm4 Cation Channel Expression in Human Cerebral Infarcts.

The nonselective monovalent cation channel transient receptor potential melastatin 4 (Trpm4) is transcriptionally upregulated in neural and vascular cells in animal models of brain infarction. It associates with sulfonylurea receptor 1 (Sur1) to form Sur1-Trpm4 channels, which have critical roles in cytotoxic edema, cell death, blood-brain barrier breakdown, and vasogenic edema. We examined Trpm4 expression in postmortem brain specimens from 15 patients who died within the first 31 days of the onset of focal cerebral ischemia. We found increased Trpm4 protein expression in all cases using immunohistochemistry; transcriptional upregulation was confirmed using in situ hybridization of Trpm4 messenger RNA. Transient receptor potential melastatin 4 colocalized and coassociated with Sur1 within ischemic endothelial cells and neurons. Coexpression of Sur1 and Trpm4 in necrotic endothelial cells was also associated with vasogenic edema indicated by upregulated perivascular tumor necrosis factor, extravasation of serum immunoglobulin G, and associated inflammation. Upregulated Trpm4 protein was present up to 1 month after the onset of cerebral ischemia. In a rat model of middle cerebral artery occlusion stroke, pharmacologic channel blockade by glibenclamide, a selective inhibitor of sulfonylurea receptor, mitigated perivascular tumor necrosis factor labeling. Thus, upregulated Sur1-Trpm4 channels and associated blood-brain barrier disruption and cerebral edema suggest that pharmacologic targeting of this channel may represent a promising therapeutic strategy for the clinical management of patients with cerebral ischemia.

Advance and prospect in studies on anaphylactoid reaction of traditional Chinese medicine injections

Because of the rapid action and high bioavailability, traditional Chinese medicine injections (TCMIs) had been widely used in clinical critical field. In recent years, with the increasing reports of clinical adverse reaction, more and more attention was paid to them, and acute allergic reaction was the main adverse reaction. Acute allergic reaction included type-I anaphylaxis reaction and anaphylactoid reaction, the latter had been found in a variety of TCMIs and accounted for 77% of adverse reaction. But the mechanism of anaphylactoid reaction was not completely understood, the standard animal model for TCMIs was not established, and the technical guidance for anaphylactoid reaction was not formulated. Thus the three aspects included mechanism, evaluation index and evaluation methods of TCMIs for anaphylactoid were reviewed. Five ways including direct stimulating pathway, complement pathway, coagulation pathway, kallikrein-kinin pathway and acute allergic pathway were the main mechanism of anaphylactoid reaction; whole animal model and cell model were the main evaluation methods; the occurrence index and effect index were reviewed for the evaluation index analysis.

A Meta-Analysis of Mesenchymal Stem Cells in Animal Models of Parkinson's Disease.

Multiple studies have been performed to evaluate the effects of mesenchymal stem cells (MSCs) in animal models of Parkinson's disease (PD). We performed a meta-analysis to estimate the treatment effect of unmodified MSCs on behavioral outcomes in preclinical studies of PD. We performed a systematic literature search to identify studies that used behavioral testing to evaluate the treatment effect of unmodified MSCs in PD models. Meta-analysis was used to determine pooled effect size for rotational behavior and limb function, and meta-regression was performed to explore sources of heterogeneity. Twenty-five studies, including three delivery routes, a wide range of doses, and multiple PD models, were examined. Significant improvement was seen in the pooled standardized mean difference (SMD) for both rotational behavior [SMD: 1.24, 95% confidence interval (95% CI): 0.84, 1.64] and limb function (SMD: 0.84, 95% CI: 0.01, 1.66). Using meta-regression, intravenous administration and higher dose had a larger effect on limb function. Treatment with MSCs improves behavioral outcomes in PD models. Our analyses suggest that MSCs could be considered for early-stage clinical trials in the treatment of PD.

Influence of overexpression of SOCS2 on cells of DN rat.

To explore the influence and mechanism of overexpression of SOCS2 on diabetic nephropathy (DN) rats and cells. STZ was used to induce male SD rats and SOCS2 was injected into left renal vein. Rats were divided into DN group, DN-Ad-null group and DN-Ad-SOCS2 group. Glucose with high and normal concentration was used to culture HBZY-1 cells and then transfect Ad-SOCS2. HG group, HG-Ad-null group, HG-Ad-SOCS2 group, CG group, CG-Ad-null group, and CG-Ad-SOCS2 group were created. The expression of inflammatory cytokines (MCP-1, TNF-α and IL-6) in kidney tissue of rats, fibrosis related protein (FN, Collagen IV and TGF-β) in kidney tissue and cells of rats, and JAK/STAT signaling pathway related proteins (p-JAK2 and p-STAT3) were tested by western blot. ELISA was used to test the expression of inflammatory cytokines (TNF-α and IL-6) in cells. The expression of inflammatory cytokines in DN rats (MCP-1, TNF-α and IL-6) and cell (TNF-α and IL-6) were increased (P<0.01) significantly. However, SOCS2 could decrease the overexpression of mediated inflammatory cytokines in DN animal models and cell models (P<0.01). The expression of fibrosis related protein in DN rats and cells increased while SOCS2 decreased the overexpression of mediated fibrosis related protein in DN model rats and cells (P<0.01). The expression of JAK/STAT pathway related protein in both DN rats and cells increased and the JAK/STAT signaling pathway was activated. Yet, SOCS2 obviously suppressed the expression of the JAK/STAT signaling pathway as well as the related proteins (p-JAK2 and p-STAT3) in both DN rats and cells. The overexpression of SOCS2 can decrease the expression of inflammatory cytokines and fibrosis related proteins in DN rats and cells, and meanwhile suppress the activation of JAK/STAT signaling pathway mediated by DN.