Reversal of acute and chronic synovial inflammation by anti- transforming growth factor beta

Transforming growth factor beta (TGF-beta) induces leukocyte recruitment and activation, events central to an inflammatory response. In this study, we demonstrate that antagonism of TGF-beta with a neutralizing antibody not only blocks inflammatory cell accumulation, but also tissue pathology in an experimental model of chronic erosive polyarthritis. Intraarticular injection of monoclonal antibody 1D11.16, which inhibits both TGF-beta 1 and TGF-beta 2 bioactivity, into animals receiving an arthropathic dose of bacterial cell walls significantly inhibits arthritis. Inhibition was observed with a single injection of 50 micrograms antibody, and a 1-mg injection blocked acute inflammation > 75% compared with the contralateral joints injected with an irrelevant isotype control antibody (MOPC21) as quantitated by an articular index (AI = 0.93 +/- 0.23 for 1D11.16, and AI = 4.0 +/- 0 on day 4; p < 0.001). Moreover, suppression of the acute arthritis achieved with a single injection of antibody was sustained into the chronic, destructive phase of the disease (on day 18, AI = 0.93 +/- 0.07 vs. AI = 2.6 +/- 0.5; p < 0.01). The decreased inflammatory index associated with anti-TGF-beta treatment was consistent with histopathologic and radiologic evidence of a therapeutic response. These data implicate TGF-beta as a profound agonist not only in the early events responsible for synovial inflammation, but also in the chronicity of streptococcal cell wall fragment-induced inflammation culminating in destructive pathology. Interrupting the cycle of leukocyte recruitment and activation with TGF-beta antagonists may provide a mechanism for resolution of chronic destructive lesions.     

Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia

We have studied the consequences of introducing human recombinant transforming growth factor beta 1 (hrTGF-beta 1) into synovial tissue of the rat, to begin to better understand the significance of the fact that biologically active TGF-beta is found in human arthritic synovial effusions. Within 4-6 h after the intra-articular injection of 1 microgram of hrTGF-beta 1 into rat knee joints, extensive recruitment of polymorphonuclear leukocytes (PMNs) was observed. Cytochemistry and high resolution histological techniques were used to quantitate the influx of PMNs, which peaked 6 h post-injection. In a Boyden chamber assay, hrTGF-beta 1 at 1-10 fg/ml elicited a chemotactic response from PMNs greater in magnitude than that evoked by FMLP, establishing that TGF-beta 1 is an effective chemotactic agent for PMNs in vitro as well as in vivo. That PMNs may represent an important source of TGF-beta in inflammatory infiltrates was strongly suggested by a demonstration that stored TGF-beta 1 was secreted during phorbol myristate acetate-stimulated degranulation in vitro. Acid/ethanol extracts of human PMNs assayed by ELISA contained an average of 355 ng of TGF/beta 1 per 10(9) cells potentially available for secretion during degranulation of PMNs. [3H]Thymidine incorporation in vivo and autoradiography of tissue sections revealed that widespread cell proliferation was triggered by TGF-beta 1 injection. Synovial lining cells and cells located deep within the subsynovial connective tissue were identified as sources of at least some of the new cells that contribute to TGF-beta 1-induced hyperplasia. Our results demonstrate that TGF-beta is capable of exerting pathogenic effects on synovial tissue and that PMNs may represent a significant source of the TGF-beta present in synovial effusions.     

NKT cells promote antibody-induced joint inflammation by suppressing transforming growth factor beta1 production

Although NKT cells has been known to exert protective roles in the development of autoimmune diseases, the functional roles of NKT cells in the downstream events of antibody-induced joint inflammation remain unknown. Thus, we explored the functional roles of NKT cells in antibody-induced arthritis using the K/BxN serum transfer model. NKT cell-deficient mice were resistant to the development of arthritis, and wild-type mice administrated with alpha-galactosyl ceramide, a potent NKT cell activator, aggravated arthritis. In CD1d-/- mice, transforming growth factor (TGF)-beta1 was found to be elevated in joint tissues, and the blockade of TGF-beta1 using neutralizing monoclonal antibodies restored arthritis. The administration of recombinant TGF-beta1 into C57BL/6 mice reduced joint inflammation. Moreover, the adoptive transfer of NKT cells into CD1d-/- mice restored arthritis and reduced TGF-beta1 production. In vitro assay demonstrated that interleukin (IL)-4 and interferon (IFN)-gamma were involved in suppressing TGF-beta1 production in joint cells. The adoptive transfer of NKT cells from IL-4-/- or IFN-gamma-/- mice did not reverse arthritis and TGF-beta1 production in CD1d-/- mice. In conclusion, NKT cells producing IL-4 and IFN-gamma play a role in immune complex-induced joint inflammation by regulating TGF-beta1.     

Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation

A rat model of bleomycin-induced pulmonary inflammation and fibrosis was used to examine the relationship between collagen synthesis and transforming growth factor beta (TGF-beta) production, and cellular distribution. Total lung TGF-beta was elevated within 2 h of intratracheal bleomycin administration and peaked 7 d later at levels 30-fold higher than controls. This was followed by a gradual decline with lower but persistent levels of production in the late phase of the response between 21 and 28 d later. The peak TGF-beta levels preceded the maximum collagen and noncollagen protein synthesis measured by [3H]proline incorporation into lung fibroblast explants of bleomycin-treated rats. The pattern of immunohistochemical staining localized TGF-beta initially in the cytoplasm of bronchiolar epithelium cells and subepithelial extracellular matrix. The peak of lung TGF-beta levels at 7 d coincided with intense TGF-beta staining of macrophages dispersed in the alveolar interstitium and in organized clusters. Later in the course of the response. TGF-beta was primarily associated with extracellular matrix in regions of increased cellularity and tissue repair, and coincided with the maximum fibroblast collagen synthesis. This temporal and spatial relationship between collagen production and TGF-beta production by macrophages suggests an important if not primary role for TGF-beta in the pathogenesis of the pulmonary fibrosis.     

转化生长因子β1诱导骨髓间充质干细胞向软骨细胞分化

背景:转化生长因子β1是关节软骨组织工程研究的首选生长因子,适当浓度能刺激关节软骨细胞增殖、分裂和分化.目的:建立含有转化生长因子β1的特殊诱导体系培养条件下骨髓间充质干细胞分化为软骨细胞的能力,观察诱导后的细胞形态及表型变化.方法:于兔胫骨结节内侧抽取骨髓,采用贴壁培养法分离纯化兔骨髓间充质干细胞,取第3代骨髓间充质干细胞行流式细胞仪检测鉴定其表面抗原,以含有转化生长因子β1的特殊软骨诱导体系的培养条件下对第3代骨髓间充质干细胞诱导培养21 d,诱导后与人鼻中隔软骨细胞进行比较.采用免疫组织化学法对Ⅱ型胶原进行定性检测.结果与结论:贴壁培养法可分离并纯化兔骨髓间充质干细胞,所得第3代骨髓间充质干细胞表面抗原CD44 阳性,CD34、CD45 阴性.经诱导培养21 d后细胞形态变为不规则,Ⅱ型胶原免疫组织化学染色显示可见阳性细胞.提示含有转化生长因子β1的特殊软骨诱导体系的培养条件下,骨髓间充质干细胞可以转化为软骨细胞,且与正常软骨细胞无明显差异.     

转化生长因子β3基因转染兔骨髓间充质干细胞诱导其向软骨表型的分化

背景:内源性诱导软骨分为就是通过一定的载体将目的基因整合入干细胞内,使其自行分泌诱导因子诱导自身进行分化.目的:观察将转化生长因子β3 通过腺相关病毒载体转染诱导兔骨髓间充质干细胞向软骨表型转化的能力.方法:取体外培养的第3 代骨髓间充质干细胞进行重组腺相关病毒转染,将转染后3,6,9,12 d 细胞裂解提取蛋白进行酶联免疫检测目的蛋白转化生长因子β3 的体外表达.RT-PCR,免疫印迹western blot 分别从基因和蛋白水平上检测1,2 周Ⅱ型胶原的表达,甲苯胺蓝染色检测1,2 周蛋白多糖的表达.结果与结论:重组腺相关病毒转染后,骨髓间充质干细胞可以较稳定的表达目的蛋白转化生长因子β3,并且转染成功的骨髓间充质干细胞较阴性对照组能够更好的向软骨表型转化.证实转化生长因子β3 可以腺相关病毒为载体转染骨髓间充质干细胞并诱导其向软骨表型分化.     

转化生长因子β3基因转染兔骨髓间充质干细胞诱导其向软骨表型的分化

背景：内源性诱导软骨分为就是通过一定的载体将目的基因整合入干细胞内,使其自行分泌诱导因子诱导自身进行分化。目的：观察将转化生长因子β3通过腺相关病毒载体转染诱导兔骨髓间充质干细胞向软骨表型转化的能力。方法：取体外培养的第3代骨髓间充质干细胞进行重组腺相关病毒转染,将转染后3,6,9,12d细胞裂解提取蛋白进行酶联免疫检测目的蛋白转化生长因子β3的体外表达。RT-PCR,免疫印迹westernblot分别从基因和蛋白水平上检测1,2周Ⅱ型胶原的表达,甲苯胺蓝染色检测1,2周蛋白多糖的表达。结果与结论：重组腺相关病毒转染后,骨髓间充质干细胞可以较稳定的表达目的蛋白转化生长因子β3,并且转染成功的骨髓间充质干细胞较阴性对照组能够更好的向软骨表型转化。证实转化生长因子β3可以腺相关病毒为载体转染骨髓间充质干细胞并诱导其向软骨表型分化。     

Inhibition of cytokine production by cyclosporin A and transforming growth factor beta

We investigated the ability of cyclosporin A (CsA) and transforming growth factor beta (TGF-beta) to modulate the production of TNF-alpha and TNF-beta and IFN-gamma by unseparated, nonadherent, and adherent PBMC. Treatment of unseparated PBMC with CsA resulted in a significant dose-dependent inhibition of all three cytokines ranging from greater than 90% inhibition for IFN-gamma and TNF-beta, to approximately 70% for TNF-alpha. Pretreatment of unseparated or nonadherent PBMC with TGF-beta inhibited the production of IFN-gamma by 60-70%. However, the inhibition of TNF-alpha and TNF-beta production by these cells was only minimally affected, and at 0.1-1 ng/ml TGF-beta could enhance TNF-alpha production by unseparated PBMC. In contrast, pretreatment of adherent PBMC with TGF-beta inhibited the production of TNF-alpha by approximately 60%. TGF-beta also inhibited both TNF-alpha production and tumor cell cytotoxicity mediated by murine peritoneal-derived macrophages. These observations indicate that the biological effects of CsA and TGF-beta on immune functions are of a wider range than previously reported.     

转化生长因子β3诱导骨髓间充质干细胞分化为软骨细胞

背景: 转化生长因子β是一族多肽类生长因子,胚胎形成期可诱导原始的间充质干细胞分化形成软骨组织,有研究报道转化生长因子β3和碱性成纤维细胞生长因子可促进软骨细胞的代谢和增殖.目的: 验证转化生长因子β3体外诱导骨髓间充质干细胞分化为软骨细胞的可行性.方法: 骨髓来源于髋关节手术时的松质骨碎片或于下肢骨开放性手术时收集,分离培养骨髓间充质干细胞,鉴定其表面抗原,用含体积分数10%胎牛血清以及10μg/L转化生长因子β3的条件培养基诱导,诱导后细胞通过软骨细胞特征性染色,即甲苯氨蓝染色以及Ⅱ型胶原免疫组织化学染色鉴定.结果与结论: 骨髓间充质干细胞表面抗原CD73,CD90,CD105阳性,CD14,CD34,CD45,CD106以及HLA-DR阴性.诱导后细胞形态明显改变,甲苯氨蓝以及Ⅱ型胶原染色结果阳性.提示骨髓间充质干细胞在转化生长因子β3作用下,体外可分化为软骨细胞,可以作为组织工程种子细胞的一种有效来源.     

Selective upregulation of platelet-derived growth factor alpha receptors by transforming growth factor beta in scleroderma fibroblasts

Transforming growth factor beta (TGF-beta), a multifunctional cytokine, is an indirect mitogen for human fibroblasts through platelet-derived growth factor (PDGF), particularly the A ligand-alpha receptor arm of that system. TGF-beta effects on PDGF alpha receptor expression were studied in vitro using ligand binding techniques in three human dermal fibroblast strains: newborn foreskin, adult skin, and scleroderma (systemic sclerosis, SSc). Each cell strain responded differently to TGF-beta. In newborn foreskin fibroblasts, PDGF alpha receptor number decreased in a dose-dependent manner after exposure to low concentrations of TGF-beta (0.1-1 ng/ml). Responses of normal skin fibroblasts were varied, and mean net receptor number was unchanged. Increases in PDGF alpha receptor number by TGF-beta occurred consistently with SSc fibroblasts and low concentrations of TGF-beta (0.1-1 ng/ml) were particularly stimulatory. Increased surface expression of alpha receptor subunit by TGF-beta in SSc fibroblasts correlated with increased new PDGF alpha receptor synthesis as demonstrated by radioimmunoprecipitation analysis of metabolically labeled cells and with increased steady-state levels of corresponding mRNAs. In normal adult skin fibroblasts, TGF-beta had no effect on either synthesis or mRNA expression of alpha receptor subunits. Proliferative responses to PDGF-AA after pretreatment with TGF-beta correlated positively with effects of TGF-beta on expression of alpha receptor subunit. Decreased mitogenic responses to PDGF-AA were observed in foreskin fibroblasts, small changes in responses in adult fibroblasts, and significant increases in SSc fibroblasts. Thus, costimulation with PDGF-AA and TGF-beta selectively enhanced proliferation of fibroblasts with the SSc phenotype. Immunohistochemical examination of SSc and control skin biopsies revealed the presence of PDGF-AA in SSc skin. Data obtained by ligand binding, immunoprecipitation, mRNA, and mitogenic techniques are consistent with the hypothesis that activation of the PDGF-AA ligand/alpha receptor pathway is a characteristic of the SSc fibroblast and may contribute to the expansion of fibroblasts in SSc.     

Role of transforming growth factor beta in conjunctival scarring

Glaucoma is the major cause of irreversible blindness throughout the world. Of all of the treatments that are available at present, the most effective appears to be surgery; however, excessive conjunctival scarring can lead to surgical failure. In the last decade, the introduction of the anti-metabolites mitomycin-C and 5-fluorouracil as anti-scarring treatments have greatly improved the results of glaucoma surgery, but these agents are associated with complications that can potentially result in blindness. A possible target for a more physiological approach to anti-scarring is transforming growth factor beta. This review examines the role of transforming growth factor beta in conjunctival scarring and discusses promising new ways of modifying its activity.     

Disruption of transforming growth factor beta signaling by a novel ligand-dependent mechanism

Transforming growth factor (TGF)-beta is the prototype in a family of secreted proteins that act in autocrine and paracrine pathways to regulate cell development and function. Normal cells typically coexpress TGF-beta receptors and one or more isoforms of TGF-beta, thus the synthesis and secretion of TGF-beta as an inactive latent complex is considered an essential step in regula-ting the activity of this pathway. To determine whether intracellular activation of TGF-beta results in TGF-beta ligand-receptor interactions within the cell, we studied pristane-induced plasma cell tumors (PCTs). We now demonstrate that active TGF-beta1 in the PCT binds to intracellular TGF-beta type II receptor (TbetaRII). Disruption of the expression of TGF-beta1 by antisense TGF-beta1 mRNA restores localization of TbetaRII at the PCT cell surface, indicating a ligand-induced impediment in receptor trafficking. We also show that retroviral expression of a truncated, dominant-negative TbetaRII (dnTbetaRII) effectively competes for intracellular binding of active ligand in the PCT and restores cell surface expression of the endogenous TbetaRII. Analysis of TGF-beta receptor-activated Smad2 suggests the intracellular ligand-receptor complex is not capable of signaling. These data are the first to demonstrate the formation of an intracellular TGF-beta-receptor complex, and define a novel mechanism for modulating the TGF-beta signaling pathway.     

转化生长因子β1联合血管内皮细胞生长因子体外诱导胚胎干细胞向血管内皮细胞分化

目的:观察胚胎干细胞在转化生长因子β1和血管内皮细胞生长因子体外诱导分化血管内皮细胞的能力,探讨提高诱导效率的方法。方法:实验于2004/2006在南昌大学医学院第二附属医院血液病研究所进行。实验材料:成年昆明小鼠由南昌大学医学院动物科学部提供(机构许可证号:96021),经自然交配怀孕。小鼠胚胎干细胞129×1/SvJ细胞系,购于ATCC公司。实验方法:取孕12.5～14.5d的胎鼠,制作小鼠胚胎成纤维细胞饲养层。在小鼠胚胎成纤维细胞饲养层上培养扩增胚胎干细胞。将饲养层上扩增后生长状态好的胚胎干细胞以0.25%胰酶消化,小心吹打成单个细胞悬液,以差速贴壁法将饲养层细胞去掉,按1×104L-1胚胎干细胞悬液悬滴在细胞培养皿的盖上,每滴10～20μL,不换液,3d后形成拟胚体,培养液为不含白血病抑制因子的胚胎干细胞培养液。挑选状态好的拟胚体分3组:转化生长因子β1诱导组、血管内皮细胞生长因子诱导组、转化生长因子β1 血管内皮细胞生长因子诱导组。采用RT-PCR和免疫组织化学方法证实诱导的细胞是否为内皮细胞。结果:①胚胎干细胞体外诱导生长观察:3组中拟胚体贴壁后第2天,胚体均略摊开,周围有上皮样细胞出现,第3,4天有许多卵石样细胞产生,至第6天开始出现由卵石样细胞构成的管状结构,自胚体向周围呈辐射状生长,渐呈网状,诱导时间约2周。转化生长因子β1 血管内皮细胞生长因子诱导组中产生的管样结构的拟胚体数较转化生长因子β1诱导组、血管内皮细胞生长因子诱导组多(44.67±3.88,28.17±6.08,33.00±2.68,P<0.05)。②RT-PCR法检测基因mRNA水平:3组基因表达的扩增片断分别为1086,733,265bp,与DNAmark相比较,条带位置相符。③扩增细胞的免疫组织化学染色:Ⅷ因子抗体反应显示阳性。结论:转化生长因子β1与血管内皮细胞生长因子均能诱导胚胎干细胞为内皮细胞,两者合用有可能提高诱导效率。     

转化生长因子β1与椎间盘退变的相关研究

学术背景:转化生长因子β1是蛋白多糖及胶原代谢等椎间盘细胞外基质的重要调节物质之一,有可能在腰椎间盘退变的病理过程及基因治疗中发挥作用.目的:分析转化生长因子β1的基因结构特点及其对椎间盘细胞的作用,认识转化生长因子β1在椎间盘退变的病理过程及基因治疗方面的作用.检索策略:应用计算机检索维普中文科技期刊数据库(VIP)、清华同方中文系列等数据库1995-01/2007-10的相关文章,并限定文章语言种类为中文和"English",检索词"间盘退变,转化生长因子β1,中医药"同时检索Medline数据库1995-01/2007-10期间的相关文章,检索词"ntervertebral disc degeneration, TGF-β1, Traditional Chinise Medicine"纳入标准:① 转化生长因子β1基因结构等特点文章.② 椎间盘退变、转化生长因子β1与中医药三者关联研究.排除标准:综述文献、重复研究、Meta分析类文章.文献评价:初检得到398篇文献,纳入37篇符合标准的文献.主要介绍转化生长因子β1基因的特点、转化生长因子β1对椎间盘细胞的影响、转化生长因子β1与椎间盘退变的生物治疗及中医药对转化生长因子β1表达的影响.资料综合:目前认为转化生长因子β1可通过改善退变的椎间盘细胞活性,刺激胶原基因表达来延缓椎间盘组织的退变,对退变早期的椎间盘尤其是髓核具有修复功能,可逆转椎间盘的退变.部分中药可促进椎间盘细胞转化生长因子β1的表达但机制未明.运用转基因疗法发挥转化生长因子β1对椎间盘退变性疾病的治疗在理论上可行,但现有技术还不能把转化生长因子β1安全、有效地注入人的椎间盘.结论:转化生长因子β1的结构及基因定位已明确,转化生长因子β1是转基因疗法治疗椎间盘疾病比较理想的目的基因,但真正应用于临床仍有待组织工程学等相关领域的深入研究.在中医药领域寻找促进转化生长因子β1表达的特异性效应物,有可能为椎间盘退变性疾病的治疗提供新的途径.     

灯盏花素对腹膜透析液诱导人腹膜间皮细胞转化生长因子β1的影响

背景:从不同层面了解灯盏花素阻止/延缓腹膜功能衰竭的作用及其机制,从而在临床上推广使用灯盏花素来阻止/延缓腹膜功能衰竭从而延长终末期肾脏病患者腹膜透析时间、提高透析质量、减少透析失败率,提高腹膜透析远期疗效具有广泛的应用前景。目的:观察灯盏花素对腹膜透析液诱导的人腹膜间皮细胞转化生长因子β1分泌及其增殖活性的影响。方法:体外培养人腹膜间皮细胞,分为5组:分别为对照组、腹膜透析液组、灯盏花素终浓度为5,10,20μmol/L组。检测各组上清液中转化生长因子β1的水平以及间皮细胞的增殖活性。结果与结论:腹膜间皮细胞在腹膜透析液诱导下,转化生长因子β1分泌显著增加、细胞增殖活性显著降低。灯盏花素5μmol/L组转化生长因子β1分泌低于腹膜透析液组(P<0.05),细胞增殖活性高于腹膜透析液组(P<0.05);灯盏花素10,20μmol/L组转化生长因子β1分泌显著低于腹膜透析液组(P<0.01),细胞增殖活性显著高于腹膜透析液组(P<0.01)。结果显示灯盏花素可以抑制腹膜间皮细胞转化生长因子β1分泌,拮抗腹膜透析液对腹膜间皮细胞增殖活性的抑制作用。     

Activation of transforming growth factor beta by malaria parasite-derived metalloproteinases and a thrombospondin-like molecule

Much of the pathology of malaria is mediated by inflammatory cytokines (such as interleukin 12, interferon gamma, and tumor necrosis factor alpha), which are part of the immune response that kills the parasite. The antiinflammatory cytokine transforming growth factor (TGF)-beta plays a crucial role in preventing the severe pathology of malaria in mice and TGF-beta production is associated with reduced risk of clinical malaria in humans. Here we show that serum-free preparations of Plasmodium falciparum, Plasmodium yoelii 17XL, and Plasmodium berghei schizont-infected erythrocytes, but not equivalent preparations of uninfected erythrocytes, are directly able to activate latent TGF-beta (LatTGF-beta) in vitro. Antibodies to thrombospondin (TSP) and to a P. falciparum TSP-related adhesive protein (PfTRAP), and synthetic peptides from PfTRAP and P. berghei TRAP that represent homologues of TGF-beta binding motifs of TSP, all inhibit malaria-mediated TGF-beta activation. Importantly, TRAP-deficient P. berghei parasites are less able to activate LatTGF-beta than wild-type parasites and their replication is attenuated in vitro. We show that activation of TGF-beta by malaria parasites is a two step process involving TSP-like molecules and metalloproteinase activity. Activation of LatTGF-beta represents a novel mechanism for direct modulation of the host response by malaria parasites.     

灯盏花素对腹膜透析液诱导人腹膜间皮细胞转化生长因子β1的影响

背景：从不同层面了解灯盏花素阻止/延缓腹膜功能衰竭的作用及其机制,从而在临床上推广使用灯盏花素来阻止/延缓腹膜功能衰竭从而延长终末期肾脏病患者腹膜透析时间、提高透析质量、减少透析失败率,提高腹膜透析远期疗效具有广泛的应用前景。目的：观察灯盏花素对腹膜透析液诱导的人腹膜间皮细胞转化生长因子β1分泌及其增殖活性的影响。方法：体外培养人腹膜间皮细胞,分为5组：分别为对照组、腹膜透析液组、灯盏花素终浓度为5,10,20μmol/L组。检测各组上清液中转化生长因子β1的水平以及间皮细胞的增殖活性。结果与结论：腹膜间皮细胞在腹膜透析液诱导下,转化生长因子β1分泌显著增加、细胞增殖活性显著降低。灯盏花素5μmol/L组转化生长因子β1分泌低于腹膜透析液组（P〈0.05）,细胞增殖活性高于腹膜透析液组（P〈0.05）;灯盏花素10,20μmol/L组转化生长因子β1分泌显著低于腹膜透析液组（P〈0.01）,细胞增殖活性显著高于腹膜透析液组（P〈0.01）。结果显示灯盏花素可以抑制腹膜间皮细胞转化生长因子β1分泌,拮抗腹膜透析液对腹膜间皮细胞增殖活性的抑制作用。