Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

Extracellular matrix and biomimetic engineering microenvironment for neuronal differentiation

Extracellular matrix(ECM)influences cell differentiation through its structural and biochemical properties.In nervous system,neuronal behavior is influenced by these ECMs structures which are present in a meshwork,fibrous,or tubular forms encompassing specific molecular compositions.In addition to contact guidance,ECM composition and structures also exert its effect on neuronal differentiation.This short report reviewed the native ECM structure and composition in central nervous system and peripheral nervous system,and their impact on neural regeneration and neuronal differentiation.Using topographies,stem cells have been differentiated to neurons.Further,focussing on engineered biomimicking topographies,we highlighted the role of anisotropic topographies in stem cell differentiation to neurons and its recent temporal application for efficient neuronal differentiation.

Targeting the extracellular matrix for NF1-associated neurofibroma treatment

Neurofibromatosis type 1(NF1)is one of the most common genetic disorders that predisposes patients to benign and malignant tumors of the peripheral nervous system.Plexiform and cutaneous neurofibromas are NF1-associated benign tumors.Despite their benign nature,they can cause tremendous morbidity in patients with NF1.Therapeutic drug options are limited to the MEK inhibitor,selumetinib,which is the only approved drug for pediatric patients with plexiform neurofibromas.Antifibrotic strategies have substantial therapeutic potential for NF1-associated neurofibromas.This review discusses the fibrotic features of plexiform and cutaneous neurofi-bromas focusing on the pathological composition of the extracellular matrix.It also highlights the core pathways implicated in the biochemical and biophysical regulation of the extracellular matrix remodeling in tumor imitation and progression.Finally,this review provides a brief outlook on how exploring novel vulnerabilities residing in the aberrant extracellular matrix and their underlying pathways can benefit the treatment of NF1-associated neurofibromas.

“Teaching old dogs new tricks”:targeting neural extracellular matrix for normal and pathological aging-related cognitive decline

Cognitive decline is a feature of normal and pathological aging. As the proportion of the global aged population continues to grow, it is imperative to understand the molecular and cellular substrates of cognitive aging for therapeutic discovery. This review focuses on the critical role of neural extracellular matrix in the regulation of neuroplasticity underlying learning and memory in another under-investigated "critical period": the aging process. The fascinating ideas of neural extracellular matrix forming a synaptic cradle in the tetrapartite synapse and possibly serving as a substrate for storage of very long-term memories will be introduced. We emphasize the distinct functional roles of diffusive neural extracellular matrix and perineuronal nets and the advantage of the coexistence of two structures for the adaptation to the ever-changing external and internal environments. Our study of striatal neural extracellular matrix supports the idea that chondroitin sulfate proteoglycan-associated extracellular matrix is restrictive on synaptic neuroplasticity, which plays important functional and pathogenic roles in early postnatal synaptic consolidation and aging-related cognitive decline. Therefore, the chondroitin sulfate proteoglycan-associated neural extracellular matrix can be targeted for normal and pathological aging. Future studies should focus on the cell-type specificity of neural extracellular matrix to identify the endogenous, druggable targets to restore juvenile neuroplasticity and confer a therapeutic benefit to neural circuits affected by aging.

Perspectives on the extracellular matrix in inflammatory bowel disease and bowel decellularization protocols

The extracellular matrix(ECM)is a non-cellular three-dimensional structure present in all tissues that is essential for the intestinal maintenance,function and structure,as well as for providing physical support for tissue integrity and elasticity.ECM enables the regulation of various processes involved in tissue homeostasis,being vital for healing,growth,migration and cell differentiation.Structurally,ECM is composed of water,polysaccharides and proteins,such as collagen fibers and proteoglycans,which are specifically arranged for each tissue.In pathological scenarios,such as inflammatory bowel disease(IBD),the deposition and remodeling of the ECM can be altered in relation to the homeostatic composition.IBD,such as Ulcerative colitis and Crohn’s disease,can be differentiated according to ECM alterations,such as circulating levels of collagen,laminin and vimentin neoepitopes.In this context,ECM presents parti-cularities in both physiological and pathological processes,however,exploring methods of tissue decellularization is emerging as a promising frontier for new therapeutic interventions and clinical protocols,promoting the development of new approaches to intestinal diseases.

Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit ＋ bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit ＋ bone marrow mesenchymal stem cells ＋ extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit ＋ bone marrow mesenchymal stem cells ＋ extracellular matrix gel group, followed by the polylactic glycolic acid conduit ＋ bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit ＋ bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit ＋ bone marrow mesenchymal stem cells ＋ extracellular matrix gel group. These results indicate that bridging 10-mm conduit ＋ bone marrow mesenchymal stem sciatic nerve defects with a polylactic glycolic acid cells ＋ extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was found with the polylactic glycolic acid conduit ＋ bone marrow mesenchymal stem cells ＋ extracellular matrix gel grafts than with the polylactic glycolic acid conduit ＋ bone marrow mesenchymal stem cells grafts and the autologous nerve grafts.

Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve

Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, hut cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhe-sion stage. Moreover, seeded cells were distributed throughout the material.

Correlation of pelvic floor ultrasound parameter with extracellular matrix remodeling and apoptosis in patients with stress urinary incontinence

Objective: To study the correlation of pelvic floor ultrasound parameter with extracellular matrix remodeling and apoptosis in patients with stress urinary incontinence. Methods:Patients with stress urinary incontinence who underwent surgical treatment in Tianmen First People's Hospital in Hubei Province between March 2015 and August 2017 were selected as the SUI group of the research and patients who underwent total hysterectomy due to benign uterine lesions in Tianmen First People's Hospital in Hubei Province over the same period were selected as the control group of the research. Pelvic floor ultrasonography was done before surgery to measure the bladder neck descent (BND), and pelvic floor tissue was collected after surgery to determine the contents of Col-I, Col-III, TGF-β1, MMP1, MMP9, TIMP1, E-cadherin, Bax, Bcl-2, Bcl-xL, Caspase-3 and HIF-1 . Results: The pelvic floor ultrasound parameter BND of SUI group was significantly higher than that of control group;Col-I, Col-III, TIMP1, E-cadherin, Bcl-2 and Bcl-xL contents in the pelvic floor tissue of SUI group were significantly lower than those of control group whereas TGF-β1, MMP1, MMP9, Bax, Caspase-3 and HIF-1 contents were significantly higher than those of control group;Col-I, Col-III, TIMP1, E-cadherin, Bcl-2 and Bcl-xL contents in the pelvic floor tissue of SUI group of patients with high BND were significantly lower than those of patients with low BND whereas TGF-β1, MMP1, MMP9, Bax, Caspase-3 and HIF-1 contents were significantly higher than those of patients with low BND. Conclusion: The change of pelvic floor ultrasound parameter BND in patients with stress urinary incontinence is closely related to the extracellular matrix remodeling and apoptosis in pelvic floor tissue.

Structures and Properties of Iron Matrix Composites with Tungsten Carbide Particle by EPC-V Process

In this paper the Expendable Pattern Casting with dry sand Vacuum(EPC-V) process is used to manufacture iron matrix composites with tungsten carbide particle.Microstructures of the composites layers were analyzed.The abrasive wear resistance of the composites layers were tested and compared with that of high chromium cast iron.The results show that the iron matrix composites with tungsten carbide particle have high hardness.The abrasive wear resistance of composites with tungsten carbide particle is higher than that of high chromium cast iron.The properties of the matrix materials have been improved remarkably.

Neural differentiation from pluripotent stem cells:The role of natural and synthetic extracellular matrix

Neural cells differentiated from pluripotent stem cells(PSCs), including both embryonic stem cells and induced pluripotent stem cells, provide a powerful tool for drug screening, disease modeling and regenerative medicine. High-purity oligodendrocyte progenitor cells(OPCs) and neural progenitor cells(NPCs) have been derived from PSCs recently due to the advancements in understanding the developmental signaling pathways. Extracellular matrices(ECM) have been shown to play important roles in regulating the survival, proliferation, and differentiation of neural cells. To improve the function and maturation of the derived neural cells from PSCs, understanding the effects of ECM over the course of neural differentiation of PSCs is critical. During neural differentiation of PSCs, the cells are sensitive to the properties of natural or synthetic ECMs, including biochemical composition, biomechanical properties, and structural/topographical features. This review summarizes recent advances in neural differentiation of humanPSCs into OPCs and NPCs, focusing on the role of ECM in modulating the composition and function of the differentiated cells. Especially, the importance of using three-dimensional ECM scaffolds to simulate the in vivo microenvironment for neural differentiation of PSCs is highlighted. Future perspectives including the immediate applications of PSC-derived neural cells in drug screening and disease modeling are also discussed.

Neurocircuit regeneration by extracellular matrix reprogramming

The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.

Biochemical composition of the glomerular extracellular matrix in patients with diabetic kidney disease

In the glomeruli,mesangial cells produce mesangial matrix while podocytes wrap glomerular capillaries with cellular extensions named foot processes and tether the glomerular basement membrane(GBM).The turnover of the mature GBM and the ability of adult podocytes to repair injured GBM are unclear.The actin cytoskeleton is a major cytoplasmic component of podocyte foot processes and links the cell to the GBM.Predominant components of the normal glomerular extracellular matrix(ECM)include glycosaminoglycans,proteoglycans,laminins,fibronectin-1,and several types of collagen.In patients with diabetes,multiorgan composition of extracellular tissues is anomalous,including the kidney,so that the constitution and arrangement of glomerular ECM is profoundly altered.In patients with diabetic kidney disease(DKD),the global quantity of glomerular ECM is increased.The level of sulfated proteoglycans is reduced while hyaluronic acid is augmented,compared to control subjects.The concentration of mesangial fibronectin-1 varies depending on the stage of DKD.Mesangial type III collagen is abundant in patients with DKD,unlike normal kidneys.The amount of type V and type VI collagens is higher in DKD and increases with the progression of the disease.The GBM contains lower amount of type IV collagen in DKD compared to normal tissue.Further,genetic variants in theα3 chain of type IV collagen may modulate susceptibility to DKD and end-stage kidney disease.Human cellular models of glomerular cells,analyses of human glomerular proteome,and improved microscopy procedures have been developed to investigate the molecular composition and organization of the human glomerular ECM.

Effects of Shikonin on Proliferation, Apoptosis, and Extracellular Matrix of Human Mesangial Cells

Objective:To investigate the effect of shikonin on the proliferation, apoptosis and extracellular matrix (ECM) of human mesangial cells (MC). Methods: MC was cultured in vitro with different concentrations of glucose (30, 50, 80 mmol/L). The cell growth was observed by using MTT method and apoptosis by using an aunexin-V-Fluos. Immunohistochemical studies for Laminin (LN), Fibronectin (FN) and type Ⅳ Collagens (Col Ⅳ) were measured. Results: Shikonin inhibited their growth (P<0.05) and apoptosis in the glycated cultured cells. Shikonin 0.05 mmol/L significantly reduced the secretion of LN, FN and Col Ⅳ from MC (P<0.05) cultured in 30, 50 and 80 mmol/L glucose. Conclusion: Shikonin could prevent or treat diabetic nephropathy (DN) and glomerulosclerosis (GS).

Role of the extracellular matrix in COVID-19

An outbreak of coronavirus disease 2019(COVID-19)has spread globally,with over 500 million cases and 6 million deaths to date.COVID-19 is associated with a systemic inflammatory response and abnormalities of the extracellular matrix(ECM),which is also involved in inflammatory storms.Upon viral infection,ECM proteins are involved in the recruitment of inflammatory cells and interference with target organ metabolism,including in the lungs.Additionally,serum biomarkers of ECM turnover are associated with the severity of COVID-19 and may serve as potential targets.Consequently,understanding the expression and function of ECM,particularly of the lung,during severe acute respiratory syndrome of the coronavirus 2 infection would provide valuable insights into the mechanisms of COVID-19 progression.In this review,we summarize the current findings on ECM,such as hyaluronic acid,matrix metalloproteinases,and collagen,which are linked to the severity and inflammation of COVID-19.Some drugs targeting the extracellular surface have been effective.In the future,these ECM findings could provide novel perspectives on the pathogenesis and treatment of COVID-19.

Correlation of extracellular matrix metalloproteinase inducer expression with inflammatory response and MMPs/TIMPs in patients with myocardial infarction

Objective:To study the correlation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression with inflammatory response and matrix metalloproteinases (MMPs) /TIMPs in patients with myocardial infarction.Methods: The patients who were diagnosed with acute myocardial infarction and the patients who were diagnosed with stable angina pectoris in the Second People's Hospital of Juancheng County between March 2014 and December 2017 were selected as the AMI group and SAP group respectively, and the healthy volunteers who received physical examination during the same period were selected as the control group. Peripheral blood was collected to detect the expression of EMMPRIN, and serum was collected to determine the contents of inflammatory cytokines and MMPs/TIMPs. Results: Peripheral blood EMMPRIN expression as well as serum ICAM1, VCAM1, IL-1β, IL-17, MMP2, MMP8 and MMP9 contents of AMI group and SAP group were significantly higher than those of control group whereas TGF-β1, sFGL-2, TIMP1 and TIMP2 contents were significantly lower than those of control group and the changes of above indexes in AMI group were more significant than those in SAP group. Serum ICAM1, VCAM1, IL-1β, IL-17, MMP2, MMP8 and MMP9 contents of AMI group of patients with high EMMPRIN expression were significantly higher than those of patients with low EMMPRIN expression whereas TGF-β1, sFGL-2, TIMP1 and TIMP2 contents were significantly lower than those of patients with low EMMPRIN expression.Conclusion:The high EMMPRIN expression in peripheral blood of patients with myocardial infarction can aggravate the inflammatory response and destroy the balance of MMPs/TIMPs.

Hippocampal Neuron-Derived Extracellular Matrix Coated Nanofibrous Scaffold for Neural Tissue Engineering

The aim of this study is to prepare poly-L-lactide(PLLA)electrospun nanofibrous scaffolds coated with hippocampal neuron-derived extracellular matrix(N-ECM)and construct a novel neural tissue engineering scaffold.Neonatal rat hippocampal neurons were seeded on PLLA nanofibers,and then decellularized to derive a cell-free extracellular matrix loaded N-ECM/PLLA modified scaffolds.The morphology and ingredients of N-ECM/PLLA were observed by scanning electron microscopy(SEM)and immunofluorescence staining respectively,and the cytocompatibility of the composite scaffolds was characterized by cell count kit-8(CCK-8)assay.The N-ECM was clearly identified loading on scaffolds when being imaged via SEM and immunofluorescence staining results showed that the N-ECM was made up of fibronectin and laminin.Most importantly,compared with tissue culture polystyrene and pure scaffolds,N-ECM/PLLA scaffolds could effectively facilitate the proliferation of rat adrenal neuroma cells(PC12 cells),indicating their better cell compatibilities.Based on the combination of N-ECM and PLLA biomaterials,the present study has fabricated a unique and versatile neural tissue engineering scaffold,offering a new thought for future neural tissue engineering.

Relationship of MMPs/TIMPs expression and extracellular matrix component levels in uterosacral ligament with apoptosis in patients with stress urinary incontinence

Objective: To study the relationship of MMPs/TIMPs expression and extracellular matrix component levels in uterosacral ligament with apoptosis in patients with stress urinary incontinence (SUI). Methods: A total of 48 patients who were diagnosed with stress urinary incontinence and received surgical treatment in Zigong First People's Hospital between May 2011 and October 2016 were selected as SUI group, and 30 patients who received vaginal hysterectomy for benign tumor during the same period were selected as control group. The uterosacral ligament was collected during operation to determine the mRNA expression of MMPs/TIMPs and apoptosis genes as well as the levels of extracellular matrix components. Results: MMP1, MMP2, MMP9, MMP14, Bax, Caspase-3, Caspase-9 and LC3-II mRNA expression in uterosacral ligament of SUI group were significantly higher than those of control group while TIMP1, TIMP2 and TIMP3 mRNA expression as well as Col-I, Col-III, Elastin, PYD and Fibulin-5 levels were significantly lower than those of control group;Bax, Caspase-3, Caspase-9 and LC3-II mRNA expression in uterosacral ligament were positively correlated with MMP1, MMP2, MMP9 and MMP14 mRNA expression, and negatively correlated with TIMP1, TIMP2 and TIMP3 mRNA expression as well as Col-I, Col-III, Elastin, PYD and Fibulin-5 levels. Conclusion: The excessive apoptosis in uterosacral ligament of patients with stress urinary incontinence is related to the imbalance of MMPs/TIMPs and the excessive degradation of extracellular matrix components.

Ultrasonic quantitative evaluation of pelvic floor characteristics in patients with stress urinary incontinence and the correlation with extracellular matrix remodeling and apoptosis

Objective: To study the ultrasonic quantitative evaluation of pelvic floor characteristics in patients with stress urinary incontinence and the correlation with extracellular matrix remodeling and apoptosis. Methods: Patients with stress urinary incontinence who received surgical treatment in Xuzhou Central Hospital between February 2015 and April 2017 were selected as the SUI group of the research, female healthy volunteers who received physical examination during the same period were selected as the control group A of the research, and patients who received total hysterectomy for benign disease during the same period were selected as the control group B of the research. The ultrasound parameters of pelvic floor characteristics of SUI group and control group A were determined before surgery, and the contents of collagen metabolism indexes, extracellular matrix metabolism indexes and apoptosis genes of SUI group and control group B were determined after surgery. Results:Pelvic floor ultrasound parameters BND, R-RVA, V-RVA and UR levels of SUI group were higher than those of control group A;Col-I and Col-II contents as well as Fibulin-5, LOX and LOXL1 mRNA expression in pelvic floor tissue of SUI group were significantly lower than those of control group B and negatively correlated with pelvic ultrasound parameter BND while ICTP content as well as Calpain1, Calpain2, Caspase-3, LC3-II and Beclin-1 mRNA expression was significantly higher than those of control group B and positively correlated with pelvic floor ultrasound parameter BND. Conclusion: The patients with stress urinary incontinence have the ultrasonic characteristics of weak pelvic support and enhanced urethral activity, and the abnormal collagen metabolism and excessive apoptosis are closely related to the changes of pelvic floor.

Correlation of annexin A2 expression with epithelial-mesenchymal transition and extracellular matrix degradation in bile duct carcinoma

Objective: To investigate the correlation of annexin A2 expression with epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) degradation in bile duct carcinoma. Methods: A total of 60 patients with primary bile duct carcinoma who accepted bile duct carcinoma laparotomy in our hospital between April 2009 and May 2017 were selected. The bile duct carcinoma tissue and adjacent normal tissue were kept during operation and enrolled in bile duct cancer group (n=60) and normal control group (n=60). The protein expression of annexin A2, EMT marker molecules, MMPs subtypes and TIMPs subtypes in two groups of specimens were detected, and Pearson test was used to evaluate the correlation of annexin A2 expression with EMT and ECM degradation in bile duct carcinoma tissue. Results: Annexin A2 expression in bile duct cancer group was higher than that in normal control group;E-cadherin, β-catenin and syndecan-1 protein expression in bile duct cancer group were lower than those in control group whereas P-cadherin and Vimentin protein expression were higher than those in normal control group;MMP-2, MMP-7 and MMP-9 protein expression in bile duct cancer group were higher than those in normal control group whereas TIMP-1 and TIMP-2 protein expression were lower than those in normal control group. Pearson test showed that the annexin A2 expression in bile duct carcinoma was directly correlated with the protein expression of EMT marker molecules, MMPs subtypes and TIMPs subtypes. Conclusion: annexin A2 increases in bile duct carcinoma, and it can regulate EMT and ECM degradation process to affect the disease outcome.