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简介：AbstractAcute kidney injury (AKI), characterized by acute renal dysfunction, is an increasingly common clinical problem and an important risk factor in the subsequent development of chronic kidney disease (CKD). Regardless of the initial insults, the progression of CKD after AKI involves multiple types of cells, including renal resident cells and immune cells such as macrophages. Recently, the involvements of macrophages in AKI-to-CKD transition have garnered significant attention. Furthermore, substantial progress has also been made in elucidating the pathophysiological functions of macrophages from the acute kidney to repair or fibrosis. In this review, we highlight current knowledge regarding the roles and mechanisms of macrophage activation and phenotypic polarization, and transdifferentiation in the development of AKI-to-CKD transition. In addition, the potential of macrophage-based therapy for preventing AKI-to-CKD transition is also discussed.

简介：AIM:ToexplorethemolecularmechanismsinlensdevelopmentandthepathogenesisofPetersanomalyinSmad4defectivemice.METHODS:Le-CretransgenicmouselinewasemployedtoinactivateSmad4inthesurfaceectodermselectively.PathologicaltechniqueswereusedtorevealthemorphologicalchangesoftheanteriorsegmentinSmad4defectiveeye.ImmunohistochemicalstainingwasemployedtoobservetheexpressionofE-cadherin,Ncadherinanda-SMAinanteriorsegmentofSmad4defectivemiceandcontrolmiceatembryonic(E)day16.5.Real-timequantitativepolymerasechainreaction(qPCR)wasperformedtodetecttheexpressionofSnail,Zeb1,Zeb2andTwist2inlensofSmad4defectivemiceandcontrolmiceatE16.5.RESULTS:ConditionaldeletionofSmad4oneyesurfaceectodermresultedincorneaidysplasia,iridocornealangleclosure,corneolenticularadhesionsandcataractresemblingPetersanomaly.LossofSmad4functioninhibitedE-cadherinexpressioninthelensepitheliumcellsandcorneaiepitheliumcellsinSmad4defectiveeye.ExpressionofN-cadherinwasupregulatedincorneaiepitheliumandcorneaistroma.BothE-cadherinandN-cadherinweredown-regulatedatthefuturetrabecularmeshworkregioninmutanteye.TheqPCRresultsshowedthattheexpressionofTwist2wasincreasedsignificantlyinthemutantlens(P<0.01).CONCLUSION:Smad4isessentialtoeyedevelopmentandlikelyacandidatepathogenicgenetoPetersanomalybyregulatingepithelial-mesenchymaltransition.Twist2canberegulatedbySmad4andplaysanessentialroleinlensdevelopment.

简介：Objective:Theaimofthepresentstudywastoanalyzetheprognosticfactorsinpatientswithhepatoblastoma(HB)inoursinglecenterandtoevaluateperiostin(POSTN)expressioninHBanditsassociationwithclinicopathologicalvariables.Inaddition,theunderlyingmechanismofhowPOSTNpromotesHBprogressionwasdiscussed.Methods:POSTNexpressionwasinvestigatedinHBtumorsbyimmunohistochemistry(IHC),immunofluorescence(IF)andWesternblot(WB).TheassociationamongPOSTNexpression,clinicopathologicalfeaturesandoverallsurvival(OS)wasalsoevaluated.ThemigrationandadhesionabilityofHBcellsweremeasuredusingchemotaxisandcell-matrixadhesionassays,respectively.Epithelial-mesenchymaltransition(EMT)-associatedmarkersandactivationoftheERKpathwayweredetectedbyWB.Results:HBpatientshadpoorprognosiswhichdisplayedlymphnodemetastasis,vascularinvasion,POSTNandvimentinexpression.POSTNexpressionwasalsoassociatedwithlymphnodemetastasis.Furthermore,overexpressedPOSTNpromotedmigrationandtheadhesiveabilityofHBcellsinvitro.Inaddition,wedemonstratedthatPOSTNactivatedtheMAPK/ERKpathway,upregulatedtheexpressionofSnailanddecreasedtheexpressionofOVOL2.Finally,POSTNpromotedtheexpressionofEMT-associatedmarkers.Conclusions:POSTNmightmodulateEMTviatheERKsignalingpathway,therebypromotingcellularmigrationandinvasion.OurstudyalsosuggeststhatPOSTNmayserveasatherapeuticbiomarkerinHBpatients.

简介：AbstractBackground:Epithelial to mesenchymal transition (EMT) is a key process in determining distant metastasis and intra-hepatic dissemination of hepatocellular carcinoma (HCC). Follistatin (FST) family members are considered to be an attractive therapeutic targets and prognostic indicators in cancers. As a derivative of FST, Follistatin Like 5 (FSTL5) may play a similar role in HCC cells. This study aimed to investigate the expression and function of FSTL5 in HCC and its role in EMT.Methods:FSTL5, E-cadherin and vimentin in HCC, and paracancerous tissues were detected by immunohistochemistry. Correlation of FSTL5 expression with overall survival was assessed. The proliferation and invasion of HCC cell lines SK-Hep1 and MHCC-LM3 were analyzed by cell counting kit-8 and Transwell assays. The expression of FSTL5, E-cadherin, and vimentin in HCC cells was examined by polymerase chain reaction and Western blot analysis. T-test was used to analyze the difference in proliferation and invasion ability between groups. The Spearman rank correlation test was used to detect the correlation between the expression of FSTL5 and E-cadherin or vimentin.Results:The expression of FSTL5 in HCC was lower than that in paracancerous tissues (9.97% vs. 82.55%, χ2 = 340.15, P < 0.001). Patients with high FSTL5 expression had a better prognosis (χ2= 8.22, P= 0.004) and smaller tumor diameter (χ2 = 45.52, P < 0.001), less lymph node metastasis (χ2 = 5.58, P= 0.02), earlier tumor node metastasis stage (χ2 = 11.29, P= 0.001), a reduced number of tumors (χ2 = 5.05, P= 0.02), lower alpha-fetoprotein value (χ2 = 24.36, P < 0.001), more probability of hepatitis carrying (χ2 = 40.9, P < 0.001), and better liver function grade (χ2 = 5.21, P = 0.02). Immunohistochemistry showed that FSTL5 expression in HCC tissues was positively correlated with E-cadherin expression (r = 0.38, P < 0.001) and negatively correlated with vimentin expression (r = -0.385, P < 0.001). Furthermore, over-expression of FSTL5 up-regulated the expression of E-cadherin and down-regulated the expression of vimentin in SK-Hep1 (negative control [NC] vs. FSTL5-interfering group [Lv-FSTL5]: E-cadherin [t= 45.03, P < 0.001], vimentin [t= 67, P < 0.001]) and MHCC-LM3 (NC vs. Lv-FSTL5: E-cadherin [t = 50, P < 0.001], vimentin [t = 72.75, P < 0.001]) cells at mRNA level. The same as protein level. In addition, the over-expression of FSTL5 inhibited the proliferation (NC vs. Lv-FSTL5: SK-Hep1, 3 d [t = 7.324, P = 0.018], 4 d [t = 6.23, P = 0.021], 5 d [t= 10.21, P= 0.003]; MHCC-LM3, 3 d [t= 4.32, P= 0.037], 4 d [t= 7.49, P= 0.012], 5 d [t= 9.3661, P = 0.009]) and invasion (NC vs. Lv-FSTL5: SK-Hep1, t= 21.57, P < 0.001; MHCC-LM3, t= 18.04, P < 0.001) of HCC cells.Conclusions:Down-regulation of FSTL5 may contribute to EMT of HCC, and FSTL5 is a potential target in the treatment of HCC.

简介：肿瘤坏死factor-α；(TNF-α；)驾驶原子factor-κ；B(NF-κ；B)激活和apoptosis正在反对小径；TNF-α的这些冲突角色的成长识别；正在困惑。这里，我们证明那发炎和apoptosis是跟随TNF-α的分阶段执行时间的事件；发信号并且表明3的cytokine(SOCS3)的suppressor的那出现表示限制进行中的NF-κ；B激活并且支持apoptosis；进一步，我们建议煽动性的疾病怎么被开始并且支撑的一个改变的看法。在vitro，TNF-α；(50ng/ml)导致了granulocyteSOCS3蛋白质，p65NF-κ的禁止的原子累积；B子单元和提高的apoptosis由DNAladdering出现在迟了的阶段的caspase-3和Bax的annexinV确实，和overexpression，而早阶段由NF-κ是显著的；B激活。相反地，由小介入RNA(siRNA)击倒的SOCS3禁止了granulocyteapoptosis并且提高了p65和5′的原子累积；在TNF-α的迟了的阶段的lipooxygenase表示；发信号。当apoptosis与SOCS3丰富被联系，我们建议那这些分叉的TNF-α；驾驶事件是分阶段执行时间的，互连的、反对控制机制并且免疫系统通过解决的中央特征之一肺的发炎。Dysregulation可以开始mucosal发炎，因此改变气喘治疗的风景。

简介：AbstractBackground:Estrogen is involved in the pathophysiological process of benign prostatic hyperplasia (BPH), in which epithelial-mesenchymal transition (EMT) plays an important role. Upregulation of aquaporin (AQP) 5, which is directly activated by estrogen, has been reported to promote EMT in multiple cells. This study aimed to examine the effects of AQP5 on estrogen-induced EMT in the prostate.Methods:Normal prostate (NP) tissue samples without any histopathological changes and BPH tissue samples with pathologically confirmed hyperplasia were obtained. An EMT cell model was subsequently established by adding estradiol (E2) to RWPE-1 cells, after which AQP5 knockdown was performed. Tissue morphological and immunohistochemical features were examined using hematoxylin-eosin and immunohistochemical staining. Western blot analysis was performed to determine the expression of AQPs, estrogen receptors, and EMT-related proteins. Cell proliferation was assessed and supernatants were collected for enzyme-linked immunosorbent assay to determine transforming growth factor-β1 (TGF-β1) concentrations. Immunofluorescence staining was performed to assess protein expressions in RWPE-1 cells.Results:BPH tissues exhibited greater EMT (TGF-β1: 1.362 ± 0.196 vs. 0.107 ± 0.067, P = 0.003; vimentin: 1.581 ± 0.508 vs. 0.221 ± 0.047, P < 0.001; E-cadherin: 0.197 ± 0.188 vs. 1.344 ± 0.088, P < 0.001), higher AQP5 (1.268 ± 0.136 vs. 0.227 ± 0.055, P < 0.001) and estrogen receptor (ER) α (1.250 ± 0.117 vs. 0.329 ± 0.134, P < 0.001) expression but lower ERβ (0.271 ± 0.184 vs. 1.564 ± 0.130, P < 0.001) expression than NP tissues. E2-stimulated cells had higher AQP5 expression (1.298 ± 0.058 vs. 1.085 ± 0.104, P = 0.049), increased cell proliferation (1.510 ± 0.089 vs.1.000 ± 0.038, P < 0.001), and EMT (TGF-β1 concentration: 0.352 ± 0.021 ng/mL vs. 0.125 ± 0.014 ng/mL, P < 0.001; vimentin: 1.641 ± 0.120 vs. 0.188 ± 0.020, P = 0.002; E-cadherin: 0.075 ± 0.030 vs. 0.843 ± 0.046, P < 0.001) than controls. E2-stimulated cells with AQP5 knockdown exhibited decreased EMT (TGF-β1 concentration: 0.223 ± 0.041 ng/mL vs. 0.352 ± 0.021 ng/mL, P= 0.016; vimentin: 0.675 ± 0.056 vs. 1.641 ± 0.120, P = 0.001; E-cadherin: 0.159 ± 0.037 vs. 0.075 ± 0.030, P = 0.040) than E2-stimulated cells with non-related small interfering RNA (siRNA).Conclusion:Our findings suggest that estrogen induces BPH possibly by promoting AQP5 expression. Hence, AQP5 might be a novel target for modulating EMT in prostate epithelial cells.

简介：AIMTo评估人的透镜上皮房间apoptosis并且对femtosecond激光在有到N3的N2的帮助奔流外科(FLACS).METHODSSixty奔流病人根据LOCSIII上演的femtosecond激光导致的间充质的转变(EMT)上皮在这研究被注册并且随机把组划分了成三：FLACS1组(由有LenSx的FLACS的奔流外科)，FLACS2组(由有LensAR的FLACS的奔流外科)和用手的组(由phacoemulsification的奔流外科)。在二个FLACS组的病人由LenSx或LensAR激光系统执行了前面的capsulotomy。在用手的组的病人被执行连续曲线的capsulorrhexis(CCC)手工地。恰好在从眼睛移动了以后，前面的囊被修理。在奔流surgery.RESULTSThe囊优势被病理学的染色在用手的capsulotomy在二个FLACS组和光滑的边看不规则和粗糙以后，染色的Hematoxylin-eosine，immunofluorescence染色和即时PCR被执行以便观察人的透镜上皮房间变化。有部分肿、破坏的原子核的房间配置的不规则在二个FLACS组被观察。Femtosecond激光能比手工地执行的CCC在人的透镜上皮房间导致显著地更高的房间apoptosis(P<0.05)。透镜上皮房间apoptosis根据皮尔森关联分析与femtosecond激光持续时间被相关。在二个FLACS组的减少的N-cadherin表示，alpha-SMA和FSP-1水平证明房间EMT.CONCLUSIONFemtosecond激光的抑制可以影响在剥的中央透镜囊下面的透镜上皮房间的apoptosis和EMT。

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简介：AbstractBackground:MicroRNA-20a (miR-20a) is dysregulated in many types of malignancies, including human hepatocellular carcinoma (HCC), but its expression level and functional significance in HCC are still disputed. We aimed to study the role of miR-20a-5p in HCC and its downstream molecular mechanisms.Methods:We used real-time polymerase chain reaction to detect the expression of miR-20a-5p and runt-related transcription factor 3 (RUNX3) in HCC and paraneoplastic tissue, transfected Huh7 and highly metastatic human hepatocellular carcinoma (MHCC97H) cells. A live cell workstation was used to observe the proliferation and migration of transfected cells. The invasiveness of transfected cells was verified by Transwell assay. Cell apoptosis was detected by flow cytometry. The expression levels of proteins after transfection were measured using simple western immunoblot measurements. Gene expression profiles between HCC and normal samples were obtained from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were processed by the database for annotation, visualization and integrated discovery. Potential target genes of miR-20a-5p were predicted to further investigate how miR-20a-5p regulates epithelial-mesenchymal transition (EMT) in HCC.Results:MiR-20a-5p was significantly highly expressed in HCC tissues, and overexpression of miR-20a-5p significantly promoted HCC cell proliferation, migration, and invasion and inhibited apoptosis in vitro. The protein expression of E-cadherin was decreased and that of vimentin was increased after overexpression of miR-20a-5p in HCC cells. We discovered the intersection of genes from miRDB, miR TarBase, and TargetScan, obtained 397 target genes and finally focused on RUNX3. RUNX3 was not only reduced in HCC specimens but also drastically reduced in HCC cells overexpressing miR-20a-5p. RUNX3 expression decreased with elevated miR-20a-5p, which activated downstream EMT signaling and promoted cell proliferation, migration, and invasion.Conclusions:Since RUNX3 is involved in EMT in HCC, as proven by previous research, our findings provide further evidence for a novel regulatory pathway comprising the miR-20a/RUNX3/EMT axis that upregulates EMT signaling and enhances the migration of HCC cells.

简介：AbstractBackground:Although increasing abnormal expression of circular RNAs (circRNAs) has been revealed in various cancers, there were a small number of studies about circRNAs in gastric cancer (GC). Here, we explored the expression and function of a novel circRNA, circ_0049447, in GC.Methods:A total of 80 GC tissues and non-tumorous tissues were collected from the First Affiliated Hospital of China Medical University. And all cells were cultured with 10% fetal bovine serum and incubated at 37°C and 5% CO2. The expression of circ_0049447 was quantified by real-time polymerase chain reaction. The biological function of circ_0049447 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) was evaluated by cell counting kit-8 (CCK-8), colony formation assay, transwell migration and invasion assay, and Western blotting. Luciferase report assay was used to verify the direct binding between circ_0049447 and predicted microRNA (miRNA). Furthermore, a xenograft mouse model was used to validate the function of circ_0049447 in vivo.Results:We demonstrated that circ_0049447 was downregulated in GC (P < 0.001). The area under the receiver operating characteristic curve reached 0.838, while sensitivity was 82.3% and specificity was 77.2%. CCK-8 and colony formation assay showed that overexpression of circ_0049447 could inhibit the proliferation (P < 0.05). Transwell migration and invasion assay showed upregulated circ_0049447 could impede migration in GC cells (P < 0.05). In addition, overexpression of circ_0049447 could impede GC cell EMT. Upregulation of miR-324-5p in GC specimens and direct binding between miR-324-5p with circ_0049447 proven by luciferase reporter assay indicated that circ_0049447 may inhibit GC by sponging certain miRNA.Conclusion:Circ_0049447 acts as a tumor suppressor in GC through reducing proliferation, migration, invasion, and EMT, and it is a promising biomarker for diagnosis.

简介：AbstractBackground:When utilizing the retrosigmoid approach (RA), accurately identifying the transverse and sigmoid sinus transition (TSST) is a key procedure for neurosurgeons, especially in developing countries restricted by the lack of expensive devices, such as the neural navigation system and the three-dimensional volumetric image-rendered system. Before operations, a computed tomography scan is a common and cost-effective method of checking patients who suffer lesions located at the cerebellopontine angle. Therefore, we present a technique using only high-resolution computed tomography to identify the transverse and sigmoid sinus transition.Methods:This retrospective study included 35 patients who underwent retrosigmoid approach operations to resect an acoustic neurinoma with the assistance of our technique. In brief, our technique contains 4 steps: (1) All patients’ 1-mm, consecutive, high-resolution computed tomographic images that clearly displayed landmarks, such as the inion, lambdoid suture, occipitomastoid suture, and the mastoid emissary foramen, were investigated initially. (2) We selected two particular slices (A and B) among all of these high-resolution computed tomographic images in which scanning planes were parallel with the line drawn from the root of the zygoma to the inion (LZI). Slice A contained both the root of the zygoma and the inion simultaneously, and slice B displayed the mastoid emissary foramen. (3) Four points (α, β, γ, δ) were arranged on slices A and B, and point α was located at the inner surface of the skull, which represents the posterior part of the sulci of the sigmoid sinus. Point β was located at the outer surface of the skull, and the line connecting them was perpendicular to the bone. Similarly, on slice B, we labeled point γ as the point that represents the posterior part of the sulci of the sigmoid sinus at the inner surface and point δ as the point located at the outer surface of the skull, and the line connecting them was also perpendicular to the bone. The distances between point β and the lambdoid suture/occipitomastoid suture and between point δ and the mastoid emissary foramen were calculated for slices A and B, respectively. (4) During the operation, a line indicating the LZI was drawn on the bone with ink when the superficial soft tissue was pushed away, and this line would cross the lambdoid suture/occipitomastoid suture. With both the crosspoint and the distance obtained from the high-resolution CT images, we could locate point β. We also used the same method to locate point δ after revealing the mastoid emissary foramen. The line connecting point β and point δ indicated the posterior border of the sigmoid sinus, and the intersection between the line and LZI indicated the inferior knee of the transverse and sigmoid sinus transition (TSST).Results:All 35 patients underwent the RA craniectomies that were safely assisted by our technique, and neither the sigmoid sinus nor the transverse sinus was lacerated during the operations.Conclusion:Our cost-effective technique is reliable and convenient for identifying the transverse and sigmoid sinus transition (TSST) which could be widely performed to guarantee the safety of RA craniectomy.

简介：AIMTo学习discoidin象我一样domaincontaining蛋白质3的效果(EDIL3)在人的透镜的增长和上皮间充质的转变(EMT)上的弄空上皮的房间(LEC).METHODSRNA干扰被用来在vitro在人的LEC禁止EDIL3的表示。房间的形态学用一台转换显微镜被观察。房间增长用EdU工具包被估计。房间移植用Transwell房间被调查，LEC的EMT用共焦的显微镜并且西方的弄污被估计。转变生长因素(TGF)小径用数据显示出的西方的blotting.RESULTSThe被调查那个silencingEDIL3表达式改变了LEC形态学并且压制了LEC增长(P<0.05)并且移植(P<0.01)。而且，西方的弄污的结果证明那EDIL3弄空减少了光滑的肌肉肌动朊的表示(-SMA)(P<0.001)并且vimentin(P<0.01)，当增加时E-cadherin的表示(P<0.001)。EDIL3弄空能压制Smad2的phosphorylation(P<0.01)并且Smad3(P<0.01)并且exracellular信号的激活调整了kinase(英皇家空军之阶级最低之兵)(P<0.05).CONCLUSIONThe调查结果显示EDIL3可能经由TGF小径在LEC参予增长和EMT并且可以是为以后的囊opacification的处理的一个潜在的治疗学的目标。

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简介：AbstractBackground:The transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/β-catenin pathway plays an important role, notably with regard to TGF-β1. Recent studies have shown that 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) inhibits TGF-β1-induced EMT, although the underlying mechanism have not yet been fully elucidated.Methods:Alveolar epithelial cells were exposed to 1α, 25(OH)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-β1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and β-catenin was analyzed by western blotting and immunofluorescence analysis. The mRNA transcript of Snail was analyzed using RT-qPCR, and matrix metalloproteinase 9 (MMP-9) activity was analyzed by gelatin zymogram. The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.Results:Both 1α, 25(OH)2D3 and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells. In addition, the Top/Fop Flash reporters showed that 1α, 25(OH)2D3 suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes, including MMP-9 and Snail, in synergy with ICG-001.Conclusion:1α, 25(OH)2D3 synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.

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简介：Interleukin-6(IL-6)-deficientmicearepronetoethanol-inducedapoptosisandsteatosisintheliver;however,theunderlyingmechanismisnotfullyunderstood.Mitochondrialdysfunctioncausedbyoxidativestressisanearlyeventthatplaysanimportantroleinthepathogenesisofalcoholicliverdisease.Therefore,wehypothesizethattheprotectiveroleofIL-6inethanol-inducedliverinjuryismediatedviasuppressionofethanol-inducedoxidativestressandmitochondrialdysfunction.Totestthishypothesis,weexaminedtheeffectsofIL-6onethanol-inducedoxidativestress,mitochondrialinjury,andenergydepletionintheliversofIL-6(-/-)miceandhepatocytesfromethanol-fedrats.Ethanolconsumptionleadstostrongerinductionofmalondialdehyde(MDA)inIL-6(-/-)micecomparedtowild-typecontrolmice,whichcanbecorrectedbyadministrationofIL-6.Invitro,IL-6treatmentpreventsethanol-mediatedinductionofreactiveoxygenspecies(ROS),MDA,mitochondrialpermeabilitytransition(MPT),andethanol-mediateddepletionofadenosinetriphosphate(ATP)inhepatocytesfromethanol-fedrats.AdministrationofIL-6invivoalsoreversesethanol-inducedMDAandATPdepletioninhepatocytes.Finally,IL-6treatmentinducesmetallothioneinproteinexpression,butnotsuperoxidedismutaseandglutathioneperoxidaseinculturedhepatocytes.Inconclusion,IL-6protectsagainstethanol-inducedoxidativestressandmitochondrialdysfunctioninhepatocytesviainductionofmetallothioneinproteinexpression,whichmayaccountfortheprotectiveroleofIL-6inalcoholicliverdisease.

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简介：AbstractBackground:The use of microRNAs in the therapy of kidney disease is hampered by the difficulties in their effective delivery. Microvesicles (MVs) are known as natural carriers of small RNAs. Our prior research has demonstrated that MVs isolated from mesenchymal stem cells (MSCs) are capable of attenuating kidney injuries induced by unilateral ureteral obstruction and 5/6 sub-total nephrectomy in mice. The present study aimed to evaluate the effects of miR-34a-5p (miR-34a)-modified MSC-MVs on transforming growth factor (TGF)-β1-induced fibrosis and apoptosis in vitro.Methods:Bone marrow MSCs were modified by lentiviruses over-expressing miR-34a, from which MVs were collected for the treatment of human Kidney-2 (HK-2) renal tubular cells exposed to TGF-β1 (6 ng/mL). The survival of HK-2 cells was determined using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and Annexin V-Light 650/propidium iodide (PI) assays. The expression levels of epithelial markers (tight junction protein 1 [TJP1] and E-cadherin) and mesenchymal markers (smooth muscle actin alpha (α-SMA) and fibronectin) in HK-2 cells were measured using Western blot analysis and an immunofluorescence assay. In addition, changes in Notch-1/Jagged-1 signaling were analyzed using Western blotting. Data were analyzed using a Student’s t test or one-way analysis of variance.Results:MiR-34a expression increased three-fold in MVs generated by miR-34a-modified MSCs compared with that expressed in control MVs (P < 0.01, t= 16.55). In HK-2 cells, TJP1 and E-cadherin levels decreased to 31% and 37% after treatment with TGF-β1, respectively, and were restored to 62% and 70% by miR-34a-enriched MSC-MVs, respectively. The expression of α-SMA and fibronectin increased by 3.9- and 5.0-fold following TGF-β1 treatment, and decreased to 2.0- and 1.7-fold after treatment of HK-2 cells with miR-34a-enriched MSC-MVs. The effects of miR-34a-enriched MSC-MVs on epithelial-mesenchymal transition (EMT) markers were stronger than control MSC-MVs. The effects of miR-34a-enriched MSC-MVs on these EMT markers were stronger than control MSC-MVs. Notch-1 receptor and Jagged-1 ligand, two major molecules of Notch signaling pathway, are predicted targets of miR-34a. It was further observed that elevation of Notch-1 and Jagged-1 induced by TGF-β1 was inhibited by miR-34a-enriched MSC-MVs. In addition, TGF-β1 exposure also induced apoptosis in HK-2 cells. Although miR-34a-mofidied MSC-MVs were able to inhibit TGF-β1-triggered apoptosis in HK-2 cells, the effects were less significant than control MSC-MVs (control:TGF-β1 :miR-nc-MV:miR-34a-MV = 1.3:0.6:1.1:0.9 for MTT assay, 1.8%:23.3%:9.4%:17.4% for apoptosis assay). This phenomenon may be the result of the pro-apoptotic effects of miR-34a.Conclusions:The present study demonstrated that miR-34a-over-expressing MSC-MVs inhibit EMT induced by pro-fibrotic TGF-β1 in renal tubular epithelial cells, possibly through inhibition of the Jagged-1/Notch-1 pathway. Genetic modification of MSC-MVs with an anti-fibrotic molecule may represent a novel strategy for the treatment of renal injuries.