转化生长因子β_1在肾纤维性修复中的作用

从细胞增殖角度看 ,转化生长因子 β1(TGF β1)是具有双重功能的细胞因子。其与肾纤维化的发生、发展关系密切 ,能够调节细胞外基质的合成及降解 ,并具有免疫抑制活性 ,其活性因细胞类型的不同而变化。TGF β1在肾纤维化过程中不同细胞内的信号转导机制及在不同病理阶段的信号通路尚不明确     

转化生长因子β与骨骼肌损伤修复的研究进展

肌肉的损伤修复是一个动态协调而又极其复杂的过程,TGF-β是一种内源性的生长因子,在肌肉损伤后通过重新编码肌肉细胞基因,抑制生肌细胞基因的表达,骨骼肌内TGF-β产生于损伤反应中,在损伤愈合的各个阶段均起作用并受TGF-β浓度的影响,TGF-β的生物学效应也受到其它生长因子的拮抗或协同作用,使用TGF-β阻断剂可以拮抗TGF-β进而减少肌肉纤维化,改善肌肉愈合质量。本文回顾了骨骼肌损伤修复与转化生长因子β的作用,并对转化生长因子β在肌肉损伤修复方面的应用前景进行了分析和探讨。     

转化生长因子β受体研究进展

转化生长因子β（ＴＧＦ－β）是一种多功能的细胞因子，其信号结构独特，为丝氨酸／苏氨酸激酶。Ⅱ型受体被ＴＧＦ－β激活后进一步导致Ⅰ型受体的活化，ＴＧＦ－β的信号由Ⅱ型受体和Ⅰ型受体的受体复合物转导至细胞内，以上二者合称信号受体。Ⅲ型受体的大分子蛋白多聚糖本身不参与ＴＧＦ－β的信号转导，却能间接调节ＴＧＦ－β的作用。有关肿瘤和ＴＧＦ－β受体的研究表明细胞表面ＴＧＦ－β受体的丢失与肿瘤发生相关，转染正常的信号受体基因在体外可抑制肿瘤细胞的增殖。在其他相关的疾病中，ＴＧＦ－β作用机制以及各型受体对ＴＧＦ－β作用调节机制的研究正在进行中。     

转化生长因子β受体的研究进展

转化生长因子β受体有3个亚型;Ⅰ型、Ⅱ型、Ⅲ型,其结构功能特点及在转导TGF-β信号过程中的作用机制不同,细胞在受体水平的变化影响TGF-β的功能。     

转化生长因子β1对瘢痕成纤维细胞合成细胞外基质的调节作用

目的：研究转化生长因子β1(TGF-β1)对瘢痕成纤维细胞胶原蛋白和粘连蛋白(FN)合成的影响,探讨TGF-β1与瘢痕细胞外基质(ECM)的关系。方法：采用细胞培养、VG化学染色、免疫组化、图像分析扫描和氯胺T法观察不同浓度TGF-β1对瘢痕成纤维细胞胶原蛋白及FN合成的影响。结果：TGF-β1在浓度为10-50ng／ml下能刺激胶原蛋白和FN的合成,并呈剂量效应关系;当TGF-β1浓度为100ng／ml时,作用达饱和。结论：TGF-β1可能与瘢痕形成过程中ECM的过度沉积有关。     

转化生长因子-β在病理性瘢痕形成方面的作用的研究进展

病理性瘢痕的形成是创伤后人体自我修复过程中的异常反应,随之而来的就是畸形、运动功能障碍等诸多问题。近年来,转化生长因子-β（TGF-β）及其所介导的细胞信号通路被认为在瘢痕形成方面起着重要作用,国内外对此进行了大量研究,本文总结了相关研究报道及结论,以期为后续的研究提供新的思路及参考。     

转化生长因子β与疾病的研究进展

转化生长因子β(Transforminggrowthfactorβ,TGF-β)可以调控许多细胞介导的过程,是一种与多种疾病密切相关的多功能肽类,对肿瘤发生,白内障、青光眼形成,神经组织、软组织创伤修复以及骨折愈合起着重要的作用,将会有助于各种疾病的诊断与治疗。     

转化生长因子β亚家族调控骨关节炎中的作用

背景：骨关节炎作为中国最常见的老年慢性退行性疾病之一,因其复杂的发病机制及细胞分子交流途径,目前尚未有行之有效的方法去延缓骨关节炎的进展。而转化生长因子β在早期关节的形成、骨和软骨的发育以及关节重塑各阶段发挥重要作用,是维持与调节关节稳态的关键因子之一。目的：综述近年来国内外关于转化生长因子β亚家族在骨关节炎的发生发展中所起到的调控作用,分析其在骨关节炎不同阶段所产生的影响,探究转化生长因子β在临床治疗骨关节炎上的应用前景,以期能为临床治疗方案提供参考。方法：应用计算机检索中国知网和PubMed数据库收录的相关文献,中文检索词为“骨关节炎,转化生长因子,信号通路,骨重塑,软骨退变,血管生成,治疗”,英文检索词为“Osteoarthritis,Transforming Growth Factor,Signaling Pathway,Bone Remodeling,Cartilage Degeneration,Angiogenesis,Treatment”,最终纳入57篇文献进行综述分析。结果与结论：(1)目前,关于骨关节炎复杂的发病机制尚未有统一定论,大量研究表明骨关节炎与细胞因子和信号...     

树突状细胞、转化生长因子β1与移植免疫研究进展

树突状细胞（dendrtic cell,DC)是分布广泛的抗原呈递细胞，一方面可激活静息型T细胞，启动T细胞抗原特异性免疫反应，另一方面由于未成熟DC可诱导T细胞凋亡，在移植免疫中发挥重要作用。近年研究发现转化生长因子β1（TGF－β1）不仅具有下调淋巴细胞和巨噬细胞功能等非特异性免疫抑制作用，还能抑制DC分化成熟从而诱导供者特异性移植耐受。     

转化生长因子β1与肺纤维化的研究进展

目的了解转化生长因子β1（TGF—β1）与肺纤维化的相关性及肺纤维化的治疗现状。方法应用现代信息技术，通过互联网等查阅近年来国内外相关资料并进行分析、整理、总结，对转化生长因子β1（TGF-β1）的生物学特征、TGF—β1与肺纤维化发病机制的相关性以及目前治疗肺纤维化的现状进行综述。结果转化生长因子β1（TGF—β1）在肺纤维化的发病机制中起到复杂的生物调节作用。结论深入研究转化生长因子β1（TGF—β1）与肺纤维化的发病之间的关系可以为临床上治疗肺纤维化提供新的思路。     

人表皮生长因子基因修饰细胞在创面修复中作用的研究进展

人表皮生长因子（hEGF）是人体中一种重要自分泌／旁分泌的生长因子,在创面修复过程中发挥着重要作用,然而局部应用hEGF修复创面存在诸多技术难题。基因修饰细胞技术的出现为创面局部应用hEGF提供了新的策略。本文对hEGF及其基因修饰的细胞在创面修复等领域的研究成果进行综述。     

肾上腺髓质素拮抗转化生长因子β1的促纤维化作用及其机制

目的:探讨肾上腺髓质素(AM)在人肾小管上皮细胞系(HK-2)对转化生长因子β₁(TGFβ₁)促纤维化作用的影响及机制。方法:细胞总胶原的合成和分泌以[³H]-脯氨酸掺入量及培养液内[³H]-羟脯氨酸放射活性来判断;ELISA法检测培养液中纤维连接蛋白(FN)含量;FN、IV型胶原和组织型金属蛋白酶抑制剂-1(TIMP-1)mRNA的表达采用RT-PCR法;信号蛋白Smad2及Smad6蛋白表达采用Westernblot法。结果:(1)AM在蛋白和mRNA水平均明显抑制TGFβ₁刺激的胶原和纤维连结蛋白的表达;(2)AM抑制TGFβ₁刺激的TIMP-1mRNA的上调;(3)AM(10^-8mol/L)本身对Smad2和Smad6的表达无明显影响,且对TGFβ₁刺激的Smad2的表达也无明显影响;但是可以明显上调被TGFβ₁抑制的Smad6的表达。结论:在HK-2细胞,AM通过上调抑制性Smad6的表达拮抗TGFβ₁的促纤维化作用。     

转化生长因子β信号与肌肉调控

BACKGROUND: Transforming growth factor-β signaling widely existing in cells mediates cell growth, proliferation, migration, differentiation, and apoptosis. The activation of transforming growth factor-β signaling can result in muscular dystrophy. However, there have been some contradictions regarding the effects of the transforming growth factor-β signaling on muscular dystrophy. OBJECTIVE: To summarize the latest progress in the effects of the transforming growth factor-β signaling on muscle mass and function regulation to provide the solutions for the treatment of muscular dystrophy. METHODS: A computer-based online search was conducted in PubMed and Wanfang databases from 2005 to 2015 to screen the relevant literatures using Chinese and English key words “transforming growth factor-β, muscle, regulation mechanism, treatment”. A total of 102 literatures were retrieved, and 22 eligible literatures were included, summarized, and analyzed. RESULTS AND CONCLUSION: The activation of transforming growth factor-β signaling as a common cause of most muscle disorders promotes the activation of muscle satellite cells, differentiation of myocytes, myoblast infusion, the expression of muscle-specific proteins, and the inhibition of collagen synthesis, which facilitates muscular fibrosis and scar formation. Transforming growth factor-β signaling is involved in Duchenne muscular dystrophy, spinal scoliosis, type I diabetes induced skeletal muscle regenerative disorders, myocardial and cardiac remodeling. The inhibition of transforming growth factor-β signaling may result in incomplete muscle recovery. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Inflammation and wound repair

Wound repair requires the integration of complex cellular networks to restore tissue homeostasis. Defects in wound repair are associated with human disease including pyoderma gangrenosum, a heterogeneous disorder that is characterized by unhealed wounds and chronic inflammation of unclear etiology. Despite its clinical importance, there remain significant gaps in understanding how different types of cells communicate to integrate inflammation and wound repair. Recent progress in wound and regenerative biology has been gained by studying genetically tractable model organisms, like zebrafish, that retain the ability to regenerate. The optical transparency and ease of genetic manipulation make zebrafish an ideal model system to dissect multi-cellular and tissue level interactions during wound repair. The focus of this review is on recent advances in understanding how inflammation and wound repair are orchestrated and integrated to achieve wound resolution and tissue regeneration using zebrafish.     

Expression of transforming growth factor-beta isoforms and their receptors in chronic tendinosis

Chronic tendon lesions are degenerative conditions and may represent a failure to repair or remodel the extracellular matrix after repeated micro-injury. Since TGF-β is strongly associated with tissue repair, we investigated the expression of TGF-β isoforms (β1, β2 and β3) and their 2 signalling receptors (TGF-βRI and TGF-βRII) in normal and pathological Achilles tendons. In all tissues, all 3 TGF-β isoforms and the 2 receptors were present at sites of blood vessels. Cells in the matrix showed no staining for TGF-β1 or β3, while TGF-β2 was associated with cells throughout the normal cadaver tendon. Tissue from tendons with pathological lesions showed an increase in cell numbers and percentage TGF-β2 expression. TGF-βRII showed a wide distribution in cells throughout the tissue sections. As with TGF-β2, there was an increase in the number of cells expressing TGF-βRII in pathological tissue. TGF-βRI was restricted to blood vessels and was absent from the fibrillar matrix. We conclude that despite the presence and upregulation of TGF-β2, TGF-β signalling is not propagated due to the lack of TGF-βRI. This might explain why chronic tendon lesions fail to resolve and suggests that the addition of exogenous TGF-β will have little effect on chronic tendinopathy.     

雌二醇通过调节上皮细胞系的旁分泌促进前列腺间质细胞增殖和分化

目的： 研究雌二醇通过调节上皮细胞的旁分泌对前列腺间质细胞增殖、分化和胞外基质蓄积的作用。方法： 雌二醇处理前列腺增生上皮细胞系BPH-1，用收集的条件培养液（CM）培养人前列腺间质细胞，MTT法检测细胞的增殖；用实时定量RT-PCR检测细胞中smoothelin、纤维黏连蛋白、Ⅳ型胶原和转化生长因子-β₁（TGF-β₁）mRNA的表达水平；用Western blotting检测细胞平滑肌肌球蛋白重链（SM-MHC）的表达；用放射性免疫法和ELISA分别检测Ⅳ型胶原、纤维黏连蛋白和TGF-β₁的蛋白水平。结果： 雌二醇能够上调BPH-1细胞中TGF-β₁的表达和分泌；经雌二醇刺激的BPH-1 CM能促进间质细胞的增殖；雌二醇刺激的BPH-1 CM对平滑肌细胞特异蛋白（smoothelin和SM-MHC）表达的促进作用较未经雌二醇刺激者更加明显；TGF-β₁中和抗体可以抑制BPH-1 CM对间质细胞中Ⅳ型胶原和SM-MHC的促表达作用。结论： BPH-1 可通过分泌TGF-β₁促进间质细胞的分化和胞外基质的蓄积；雌二醇可通过上调BPH-1 TGF-β₁的分泌进一步促进间质细胞的分化；雌二醇还可通过调节BPH-1分泌的某种活性因子促进间质细胞的增殖。     

Functional remodeling after vocal fold injury by small intestinal submucosa gel containing hepatocyte growth factor

A biomaterial derived from porcine small intestinal submucosa (SIS) was used in smart drug delivery and tissue remodeling. SIS suspensions were easily formulated by simple mixing with the drug of choice and formed an in situ gel upon injection into tissues, enabling them to act as protein drug depots. This study was conducted to determine whether functional remodeling of an injured vocal fold (VF) could be achieved by hepatocyte growth factor (HGF)-containing SIS in situ-forming gel after VF injury in a rabbit model. To accomplish this, we loaded HGF in SIS suspensions and observed a gradual, sustained release of HGF for at least 21 days in vitro. Evaluation of the in vivo efficacy demonstrated that the HGF and HGF-loaded SIS treated VFs showed improved mucosal healing when compared with the PBS-injected VFs. Histopathological evaluations revealed that treatment with the HGF/SIS group alone successfully ameliorated the deposition of type I collagen and increased synthesis of hyaluronic acids relative to the PBS group at three months post-injury. Functional analyses showed that the HGF/SIS group prevented deterioration of mucosal vibration and induced significant improvement in the mean viscoelastic modulus, but that other groups failed to achieve functional rescue of VF biomechanics. Additionally, the VF oscillation in the HGF/SIS group was superior to that in the HGF group. The results of this study suggest that SIS in situ gel has the potential for use as an HGF delivery carrier for enhancement of wound healing and improvement of functional remodeling following VF injury.     

转化生长因子β1降低大鼠自发性癫痫发作并抑制胶质细胞活化

 目的：观察经鼻给予转化生长因子β₁（TGF-β₁）是否能减少匹罗卡品致痫大鼠慢性自发性癫痫的发作并探讨其可能机制。方法：经鼻给予大鼠重组人TGF-β₁或等量PBS溶液,以匹罗卡品建立癫痫持续状态模型,癫痫持续状态后7 d经动态视频记录其活动,通过胶质纤维酸性蛋白(GFAP)和离子钙结合接头分子1（Iba1）免疫组化观察癫痫大鼠海马组织胶质细胞的活化,采用尼氏染色观察海马区神经元的死亡。结果：TGF-β₁有效降低自发性癫痫的平均频率、发作程度和持续时间。癫痫持续状态后14 d TGF-β₁治疗组海马区活化的胶质细胞明显少于匹罗卡品模型组（P<0.05）;TGF-β₁显著降低海马CA3区神经元的死亡(P<0.01)。结论：经鼻给予TGF-β₁可降低大鼠自发重复性癫痫发作,抑制胶质细胞活化,从而减少神经元的死亡。     

神经生长因子在糖尿病足创面组织中表达相关性的研究进展

动物实验研究证实神经生长因子（NGF）促进创面组织血管生成、血管内皮细胞再生,促进缺血创面的愈合及糖尿病创面的愈合。通过NGF在糖尿病创面表达改变的研究,有助于NGF促进糖尿病创面愈合机制的探讨,为糖尿病足创面愈合提供新的理论依据。