曲尼司特对环孢素A诱导的人肾小管上皮细胞向间充质转变的抑制作用

目的 研究曲尼司特(Tran)对环孢素A(CsA)诱导的人肾小管上皮细胞(HK-2)向间充质转变的影响,并探讨该药抗纤维化的机制.方法 所有用于实验的HK-2细胞株均为8～12代细胞,分为4组:(1)空白对照组,收获细胞,不做任何处理;(2)CsA组,加入4.2μmol/LCsA;(3)CsA+Tran组,预先加入100μmol/L Tran,作用2 h后再加入4.2 μmol/L CsA;(4)Tran组,仅加入100μmol/L Tran.72 h后于共聚焦显微镜下观察各组细胞形态学变化;用免疫荧光法以及免疫印迹法检测各组钙黏蛋白(E-cadherin)、平滑肌肌动蛋白α(α-SMA)和骨桥蛋白(OPN)的表达.结果 HK-2细胞在正常情况下表现为典型的"鹅卵石"样形态,细胞圆钝,且与邻近的细胞连接较为紧密;空白对照组和Tran组细胞表现为典型的HK-2细胞形态;CsA组细胞变狭长,甚至向周边伸出"伪足"样改变,细胞间连接较为稀疏;CsA+Tran组的细胞形态学改变有明显改善.CsA组细胞E-cadherin荧光表达强度明显弱于对照组,α-SMA、OPN荧光表达强于对照组;CsA+Tran组细胞E-cadherin荧光表达强于CsA组,α-SMA、OPN荧光表达弱于CsA组.免疫印迹检查中,CsA组细胞E-cadherin 的表达明显低于对照组,而α-SMA、OPN的表达明显高于对照组,CsA+Tran组细胞E-cadherin的表达高于CsA组,而α-SMA、OPN的表达低于CsA组.结论 曲尼司特能抑制CsA诱导的HK-2细胞由肾小管上皮向间充质细胞转化的过程,其机制可能与抑制OPN的表达有关.

Abstract：

Objective To study the effect of tranilast on cyclosporine A (CsA)-induced epithelial-to-mesenchymal transition in human renal tubular epithelial cells, and investigate the mechanism of its antifibrotic effect. Methods Cultured HK-2 cells were divided into four groups: (1)In the control group, cells were treated without any medicine; (2) The cell were treated with CsA (4. 2μmol/L) for 72 h; (3) The cells were treated with a combination of CsA (4. 2 μmol/L) and tranilast (100μmol/L); (4) The cells were treated with tranilast (100 μmol/L) alone for 72 h.Morphological changes of the cells were assessed by phase-contrast microscopy. The immunofluorescence and Western blotting were adopted to detect the expression of E-cadherin, α-SMA and OPN mRNA and proteins respectively. Results Tranilast could markedly ameliorate the morphological changes of HK-2 cells stimulated by CsA. The irmmunofluorescence staining revealed the expression of E-cadherin was markedly decreased in HK-2 cells stimulated with CsA for 72 as compared with the control group, while the expression of α-SMA and OPN was significantly higher in CsA group than the control group. The expression of E-cadherin in the CsA + Tranilast group was higher than the CsA group, while the expression of α-SMA and OPN in the CsA + Tranilast group was lower than the CsA group. Western blotting showed that protein expression level of E-cadherin in CsA group was dramatically lower than that in the control group (P＜0. 05), while that of α-SMA and OPN in CsA group was significantly higher than in the control group (P＜0.05). The protein expression level of E-cadherin in HK-2 cells in the CsA + Tranilast group was markedly higher than in the CsA group (P＜0.05), and that of α-SMA and OPN in CsA + Tranilast group was significantly lower than in the CsA group (P＜0. 05). Conclusion Tranilast can block the CsA-induced epithelialto-mesenchymal transition in HK-2 cells probably by suppressing the expression of OPN.     

曲尼司特对环孢素A诱导的人肾小管上皮细胞向间充质转变的抑制作用

Objective To study the effect of tranilast on cyclosporine A (CsA)-induced epithelial-to-mesenchymal transition in human renal tubular epithelial cells, and investigate the mechanism of its antifibrotic effect. Methods Cultured HK-2 cells were divided into four groups: (1)In the control group, cells were treated without any medicine; (2) The cell were treated with CsA (4. 2μmol/L) for 72 h; (3) The cells were treated with a combination of CsA (4. 2 μmol/L) and tranilast (100μmol/L); (4) The cells were treated with tranilast (100 μmol/L) alone for 72 h.Morphological changes of the cells were assessed by phase-contrast microscopy. The immunofluorescence and Western blotting were adopted to detect the expression of E-cadherin, α-SMA and OPN mRNA and proteins respectively. Results Tranilast could markedly ameliorate the morphological changes of HK-2 cells stimulated by CsA. The irmmunofluorescence staining revealed the expression of E-cadherin was markedly decreased in HK-2 cells stimulated with CsA for 72 as compared with the control group, while the expression of α-SMA and OPN was significantly higher in CsA group than the control group. The expression of E-cadherin in the CsA + Tranilast group was higher than the CsA group, while the expression of α-SMA and OPN in the CsA + Tranilast group was lower than the CsA group. Western blotting showed that protein expression level of E-cadherin in CsA group was dramatically lower than that in the control group (P＜0. 05), while that of α-SMA and OPN in CsA group was significantly higher than in the control group (P＜0.05). The protein expression level of E-cadherin in HK-2 cells in the CsA + Tranilast group was markedly higher than in the CsA group (P＜0.05), and that of α-SMA and OPN in CsA + Tranilast group was significantly lower than in the CsA group (P＜0. 05). Conclusion Tranilast can block the CsA-induced epithelialto-mesenchymal transition in HK-2 cells probably by suppressing the expression of OPN.     

曲尼司特对环孢素A诱导的人肾小管上皮细胞向间充质转变的抑制作用

Objective To study the effect of tranilast on cyclosporine A (CsA)-induced epithelial-to-mesenchymal transition in human renal tubular epithelial cells, and investigate the mechanism of its antifibrotic effect. Methods Cultured HK-2 cells were divided into four groups: (1)In the control group, cells were treated without any medicine; (2) The cell were treated with CsA (4. 2μmol/L) for 72 h; (3) The cells were treated with a combination of CsA (4. 2 μmol/L) and tranilast (100μmol/L); (4) The cells were treated with tranilast (100 μmol/L) alone for 72 h.Morphological changes of the cells were assessed by phase-contrast microscopy. The immunofluorescence and Western blotting were adopted to detect the expression of E-cadherin, α-SMA and OPN mRNA and proteins respectively. Results Tranilast could markedly ameliorate the morphological changes of HK-2 cells stimulated by CsA. The irmmunofluorescence staining revealed the expression of E-cadherin was markedly decreased in HK-2 cells stimulated with CsA for 72 as compared with the control group, while the expression of α-SMA and OPN was significantly higher in CsA group than the control group. The expression of E-cadherin in the CsA + Tranilast group was higher than the CsA group, while the expression of α-SMA and OPN in the CsA + Tranilast group was lower than the CsA group. Western blotting showed that protein expression level of E-cadherin in CsA group was dramatically lower than that in the control group (P＜0. 05), while that of α-SMA and OPN in CsA group was significantly higher than in the control group (P＜0.05). The protein expression level of E-cadherin in HK-2 cells in the CsA + Tranilast group was markedly higher than in the CsA group (P＜0.05), and that of α-SMA and OPN in CsA + Tranilast group was significantly lower than in the CsA group (P＜0. 05). Conclusion Tranilast can block the CsA-induced epithelialto-mesenchymal transition in HK-2 cells probably by suppressing the expression of OPN.     

曲尼司特对阿霉素肾硬化大鼠CD147表达的影响

目的探讨曲尼司特（tranilast）对阿霉素肾硬化大鼠肾组织病理变化的影响及作用机制。方法采用单侧肾切除并阿霉素尾静脉注射法建立大鼠肾小球硬化模型,20只造模大鼠随机分为模型组和曲尼司特治疗组,另设10只作为假手术组。治疗组给予曲尼司特（400mg·kg^-1·d^-1）干预,观察干预前后尿蛋白、血尿素氮（BUN）、血肌酐（SCr）的变化;观察曲尼司特给药8周后肾小球的病理改变;RT-PCR和免疫组化法观察肾小球细胞外基质金属蛋白酶诱导因子（CD147）阳性表达,并进行图像分析。结果曲尼司特治疗组蛋白尿、肾功能和病理改变较模型组有明显改善（P〈0．05）,肾小球内CD147表达较模型组显著增加（P〈0．05）。结论曲尼司特能上调CD147的表达,减轻阿霉素致肾小球硬化的病理改变。     

肾小管上皮细胞-间充质细胞转分化与肾间质纤维化

肾小管上皮细胞-间充质细胞转分化（EMT）在肾间质纤维化进程中发挥重要作用。多种细胞因子和信号转导途径参与调节EMT，其中TGF-B1／Smad信号通路发挥核心作用。肝细胞生长因子（HGF）及骨形成蛋白-7（BMP-7）可抑制EMT，减轻肾间质纤维化。激活素可能参与了EMT的进程。     

山莨菪碱对环孢素A肾毒性的保护作用

环孢素Ａ（ＣｓＡ）是目前在器官移植中防止排斥反应最常用的药物。我们观察了山莨菪碱对大鼠ＣｓＡ肾毒性的防护作用，并探讨了其可能机制。一、材料与方法１．材料健康雄性Ｗｉｓｔａｒ大鼠３０只，体重２００～３００ｇ（由江西省动物研究所提供）；ＣｓＡ注射液（由瑞...     

肝细胞生长因子对人肾小管上皮细胞转分化抑制作用初步研究

目的：晚近研究提示肝细胞生长因子（hepatocyte growth factor,HGF)具有减轻实验性肾间质纤维化的作用，但其机制尚不十分清楚；本研究目的在于探讨HGF对人肾小管上皮细胞（HKC）转分化的作用。方法：将体外培养的HKC细胞分为：（1）无血清培养对照组；（2）阳性对照组（MCP－1＋AAⅠ）；（3）HGF组（HGF浓度为0.01,0.1,1.0,10.0ng/ml);(4)MCP-1 AAⅠ HGF组（HGF浓度0.1,1.0,10.0ng/ml)。应用间接免疫荧光法检测HKC细胞内α-平滑肌肌动蛋白（α-SMA）、波形蛋白、角蛋白表达的变化。应用流式细胞技术检测α-SMA（＋）的HKC细胞百分数。结果：不同浓度HGF分别作用于HKC细胞48h后，经间接免疫荧光法测定该组HKC细胞角蛋白、波形蛋白及α－SMA抗原表达,与无血清对照组均无显著差异；流式细胞术测得HGF组α-SMA表达阳性HKC细胞百分数，与无血清对照组（平均为3.1%)也无显著差异（P＞0.05)。MCP－1＋AAⅠ培养HKC48h后α－SMA（＋）的HKC细胞平均百分数为85.6%。MCP－1＋AAⅠ＋HGF（0.1,1.0,10.0ng/ml)培养HKC48h后，α－SMA（＋）的HKC细胞百分数分别为26.7%，2.0%,13.6%，比阳性对照组明显下降（P＜0.05)。结论：（1）HGF对正常HKC细胞分化无明显影响；（2）HGF对某些因素诱导下发生的增强的HKC细胞转化可能具有显著抑制作用。     

中药抗肾小管上皮细胞间充质转分化的研究进展

肾间质纤维化（renal interstitial fibrosis,RIF）是各种慢性肾脏疾病发展到终末期肾衰竭的共同途径,以细胞外基质（extracellular matrix,ECM）在肾间质的过度积聚与沉积,以及成纤维细胞的增生为特征,是多种细胞、生长因子、细胞因子,共同参与、相互作用,最终导致ECM合成增多,降解减少,过度沉积的结果。     

己酮可可碱对肾小管上皮细胞转分化抑制作用的实验研究

目的:探讨己酮可可碱(PTX)对单侧输尿管梗阻(UUO)模型大鼠肾间质平滑肌肌动蛋白(α-SMA)表达的影响,并在体外研究其对肾小管上皮细胞转分化及其对Smad 7表达的作用.方法:将实验大鼠分为假手术组、UUO对照组和UUO PTX治疗组.用免疫组化法测定各组动物肾组织α-SMA表达.体外培养的人肾小管上皮细胞(HK-2),经TGF-β1及PTX干预后,用蛋白印迹检测α-SMA和Smad 7表达,用ELISA检测培养上清中Ⅰ型胶原含量.结果:假手术组大鼠肾组织仅血管壁α-SMA免疫染色阳性.UUO对照组第3 d、第7 d、第14 d,α-SMA表达程度分别为(2.90±0.71)%、(8.50±0.97)%、(17.9±2.70)%,PTX治疗组则分别为(2.70±0.62)%、(6.90±0.83)%、(13.8±1.9)%,术后第7 d(P<0.05)、第14 d(P<0.01)两组有统计学差异.TGF-β1(8 ng/ml)刺激HK-2细胞72 h后,α-SMA表达强度为(87.7±7.0)%,培养上清中Ⅰ型胶原浓度为(2 560.49±95.03) ng/ml;而加入PTX 10、50、100、300、500 μg/ml干预72 h后,α-SMA表达强度(F＝174.998,P<0.001)和培养上清中的Ⅰ型胶原(F＝460.883,P<0.001)呈浓度依赖性减少.在TGF-β1刺激前24 h、TGF-β1刺激后0 h、12 h、24 h、36 h或48 h后分别加入PTX(500 μg/ml),α-SMA表达强度(F＝144.131,P<0.001)和培养上清中的Ⅰ型胶原(F＝444.557,P<0.001)则呈时间依赖性减少.TGF-β1刺激的同时,分别加入PTX 10、50、100、300、500 μg/ml干预72 h后,Smad 7表达强度分别为(50.6±3.1)%、(49.4±2.9)%、(48.9±2.5)%、(51.4±1.8)%、(49.5±3.0)%,与阳性对照组(46.9±3.5)%比较无统计学差异(P＞0.05).结论:(1)PTX可减少UUO大鼠肾间质α-SMA表达;(2)在体外,PTX可抑制TGF-β1诱导的肾小管上皮细胞转分化,该作用与Smad 7表达无关,其机制有待于进一步研究.     

环孢素A对鼠肾小管上皮细胞的毒性作用

目的 研究环孢素A(CsA)对鼠肾小管上皮细胞的毒性作用及病理学机制。方法 利用体外培养实验法，将鼠肾小管上皮(NRK-52E)细胞，在体积分数95％O2／5％CO2、37℃的条件下培养24h后，用不同浓度的CsA处理48h。对细胞损伤的形态学、培养液中乳酸脱氢酶(LDH)含量及细胞的脱落死亡进行观察和检测；细胞凋亡采用TUNEL染色法检测。结果 用CsA处理48h后。NRK-52E细胞出现了空泡化、脱落以至大片死亡；培养基中LDH含量明显增高。同时，经CsA处理的部分NRK-52E细胞核出现了明显断片化，TUNEL染色阳性，发生了细胞的凋亡。CsA对NRK-52E细胞的这种毒性作用与使用剂量和时间呈正相关。结论 CsA对鼠肾小管上皮细胞的毒性作用较强。细胞凋亡可能是CsA致肾小管细胞毒性的重要病理学机制之一。     

缺氧条件下大鼠肾小管上皮细胞的离体培养及相关检测

目的 探讨缺氧条件下离体培养的肾小管上皮细胞中纤维化相关标记物结缔组织生长因子(CTGF)表达的变化,以及缺氧导致肾小管上皮细胞向间充质细胞转化(EMT)的可能性.方法采用无糖培养基在无氧环境下培养大鼠肾小管上皮细胞(NRK-52E细胞)4 h,恢复含氧环境后再分别培养6、12、24、48和72 h.用实时定量聚合酶链反应和蛋白质印迹测定各时段细胞中CTGF mRNA和CTGF表达的变化.共聚焦显微镜下观察细胞形态变化.对细胞骨架蛋白--多聚体纤维状肌动蛋白(F-actin)进行标记染色,检测缺氧对其的影响.结果 缺氧后NRK-52E细胞骨架蛋白F-actin的表达增加;NRK-52E细胞的形态由立方上皮向肌纤维母细胞转变;缺氧后,细胞中CTGF mRNA和CTGF的表达明显增高,在恢复含氧环境培养48 h时达到高峰,CTGF mRNA值为29.33±0.21,CTGF的吸光度比值为1.30±0.02.结论缺氧可导致大鼠肾小管上皮细胞中CTGF的表达增加,诱导NRK- 52E细胞发生EMT,CTGF可能是NRK-52E细胞发生EMT和纤维化的关键分子.

Abstract：

Objective To explore whether anoxia can induce expression changes in connective tissue growth factor(CTGF)in renal tubular epithelial cells(TECs)and epithelial-mesenchymal transition of TECs.Methods Rat renal TECs(NRK-52E)anoxia models were established.NRK-52E cells were exposed to anoxia for 4 h.The real-time RT-PCR,Western blotting,immunohistochemical staining were used to detect the expression of CTGF at 6,12,24,48,and 72 h in NRK-52E cells.Morphological changes and cytoskeleton remodeling in NRK-52E cells under anoxia were examined by a laser confocal microscope and BODIPYFL staining respectively.Results Under anoxia,NRK-52E cells became round,enlarged and cytoskeleton was remodeled.The expression levels of CTGF mRNA and protein were up-regulated at 6 h,reached their peak at 48 h:the expression of CTGF mRNA protein was 29.33±0.21 and 1.30±0.02 respectively.Under anoxia,NRK-52E cells underwent an epithelial-mesenchymal transition process,including cytoskeleton remodeling,and morphological changes.Conclusion Anoxia can change the expression of CTGF and other fibrosis-associated genes in NRK-52E cells,and CTGF played an important role in fibrosis process and epithelial-mesenchymal transition development in NRK-52E cells.     

Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies

BACKGROUND: In recent studies performed on cultured cells and experimental nephropathies, it has been hypothesized that tubular epithelial cells (TEC), via epithelial-mesenchymal transformation (EMT), can become collagen-producing cells. According to this theory, they should proceed through several activating steps, such as proliferation and phenotype changes, to eventually synthesize extracellular matrix (ECM). METHODS: To evaluate whether EMT operates in human TECs, 133 renal biopsies of different renal diseases were studied, analyzing by immunohistochemistry and in situ hybridization the possible expression of markers of proliferation (PCNA, Mib-1), cellular phenotype (vimentin, alpha-SMA, cytokeratin, ZO-1) and ECM production (prolyl 4-hydroxylase, HSP47, interstitial collagens). RESULTS: Independently of histological diagnosis, variable degrees of TEC positivity for PCNA (2.7 +/- 2.4 cells/field) and Mib-1 (1.9 +/- 2.3) were present. TECs expressing vimentin (1.4 +/- 4.7) and alpha-smooth muscle actin (alpha-SMA; 0.04 +/- 0.4) also were detected. It was possible to observe loss of epithelial antigens from 8 to 10% of the tubular cross sections. Moreover, TECs were stained by prolyl 4-hydroxylase (3.6 +/- 4.3), heat shock protein-47 (HSP47; 2.9 +/- 5.4), collagen type I (0.2 +/- 2.7) and type III (0.3 +/- 2.0). Collagen types I and III mRNAs were found in 0.8 to 1.4 cells/field. The number of TEC with EMT features were associated with serum creatinine and the degree of interstitial damage (P< or = 0.03), and even considering the 45 cases with mild interstitial lesions, the tubular expression of all markers remained strictly associated with renal function (P< or = 0.01). CONCLUSIONS: Our results suggest that, via transition to a mesenchymal phenotype, TEC can produce ECM proteins in human disease and directly intervene in the fibrotic processes. Moreover, the association of EMT features with serum creatinine supports the value of these markers in the assessment of disease severity.     

PINCH-1和整合素连接激酶的相互作用对人肾小管上皮细胞转分化的影响

肾小管上皮细胞间充质细胞转化(EMT)是肾间质纤维化发生发展的核心环节之一[1].转化生长因子β1(TGF-β1)具有较强的促EMT作用[2].整合素莲接激酶(ILK) 是TGF-β1诱导EMT过程中的一个关健的调节因子[3],介导细胞与细胞外基质(ECM)间的作用;也是与PINCH-1(particularly interesting new cysteine-histidine rich protein-1)有相互作用的锚定蛋白[4].     

Numb基因在大鼠肾小管上皮细胞转分化过程中的作用

目的 探讨Numb在大鼠肾小管上皮细胞转分化过程中的作用。 方法 重组人转化生长因子β1（TGF-β1）刺激大鼠近端肾小管上皮细胞(NRK52E细胞),不同浓度TGF-β1 （0、1、5、10、15、20 μg/L）作用48 h与TGF-β1 10 μg/L作用不同时间(0、24、48、72 h)后,采用RT-PCR、Western印迹和免疫荧光染色分别检测NRK52E细胞内E钙黏蛋白(E-cadherin)、α平滑肌肌动蛋白（α-SMA）和Numb 的表达。采用RNA干扰技术下调Numb表达,Western印迹观察改变Numb水平对E-cadherin、α-SMA蛋白水平的影响。 结果 TGF-β1以剂量及时间依赖的方式诱导NRK52E细胞E-cadherin 蛋白表达下调,α-SMA 蛋白表达增高。Numb蛋白的表达随TGF-β1浓度的增加而增高,在5、10、15和20 μg/L时分别为0 μg/L时的1.33倍（P = 0.024)、1.39倍（P = 0.035）、1.45倍（P = 0.025）和1.51倍（P = 0.000)。而Numb蛋白和mRNA的表达亦随TGF-β1作用时间的延长而增高,作用24 h、48 h、72 h,Numb蛋白分别为0 h的1.48倍（P = 0.046)、1.54倍（P = 0.011）、1.79倍（P = 0.028）,Numb mRNA分别为0 h的1.56倍（P = 0.012)、1.82倍（P = 0.008）、1.82倍（P = 0.002）;同时Numb的分布也发生了改变,大量聚集在胞质中。下调Numb表达可以显著抑制TGF-β1诱导的α-SMA表达上调（为Numb表达正常时的18.1%,P = 0.004）、E-cadherin表达下调（为Numb表达正常时的2.19倍,P = 0.004）。 结论 Numb可以促进肾小管上皮细胞发生转分化。     

PAX2 may induce ADAM10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition

International Urology and Nephrology - We sought to investigate the role of PAX2 in renal epithelial-to-mesenchymal transition (EMT), examining the influence of PAX2 on ADAM10 expression during...     

Involvement of renal progenitor tubular cells in epithelial-to-mesenchymal transition in fibrotic rat kidneys

Renal progenitor tubular cells (label-retaining cells [LRC]) were recently identified in normal kidneys by in vivo bromodeoxyuridine (BrdU) labeling. This study was conducted to examine the behavior of LRC in renal fibrosis. BrdU was injected intraperitoneally into normal rats daily for 7 d. After a 2-wk chase period, unilateral ureteral obstruction (UUO) was induced in these rats. In normal and contralateral kidneys, LRC were observed scattering among tubular epithelial cells. After UUO, the number of the LRC significantly increased, and most of them were positive for proliferating cell nuclear antigen (PCNA). In contrast, PCNA+ cells lacking BrdU label were rarely observed. It is interesting that LRC were detected not only in tubules but also in the interstitium after UUO. Laminin staining showed that a number of the LRC were adjacent to the destroyed tubular basement membrane. Some tubules, including LRC, lost the expression of E-cadherin after UUO. A large number of cell populations expressed vimentin, heat shock protein 47, or alpha-smooth muscle actin in the UUO kidneys, and each population contained LRC. None of the LRC was positive for these fibroblastic markers in contralateral kidneys. When renal tubules from BrdU-treated rats were cultured in the gel, some cells protruded from the periphery of the tubules and migrated into the gel. Most of these cells were BrdU+. Neither the total content of BrdU in the kidneys nor the number of LRC in bone marrow significantly changed after UUO. Collectively, these results suggest that LRC is a cell population that proliferates, migrates, and transdifferentiates into fibroblast-like cells during renal fibrosis.     

Role of JLP on the epithelial to mesenchymal transition in renal tubular epithelial cells

Objective To observe the effect of JLP on transdifferentiation of human renal proximal tubular epithelial cells (HK-2), and to investigate the role of p38 MAPK signaling pathway in this process. Methods The knock-down plasmids of JLP were constructed. HK-2 cells were randomly divided into four groups: negative control cells (Ctrl-shRNA group), knock-down jlp cells (jlp-shRNA group), negative control cells with FGF-2 treatment (FGF-2 group) and knock-down jlp cells with FGF-2 treatment(jlp-shRNA+FGF-2 group). The expressions of JLP, E-cadherin, TGF-β1, α-SMA, p-p38 MAPK protein were detected by Western blotting．After the induction of FGF-2 for 24 hours, the expressions of α-SMA, COL-I, FN were detected by immunocytochemistry. Results Compared with Ctrl-shRNA group, the expression of JLP protein was significantly down-regulated in FGF-2 group. Compared with FGF-2 group, the expressions of TGF-β1, α-SMA, p-p38 MAPK protein were significantly up-regulated, while E-cadherin protein was significantly down-regulated (P＜0.05). Compared with FGF-2 group, the expressions of α-SMA, COL-I, FN immunostaining increased markedly in jlp-shRNA+FGF-2 group. Conclusion Scaffolding protein JLP is critical in preventing EMT in the course of fibrosis through the inhibition of p-p38 activation in HK-2 cells.