吉林大学学报(医学版) ›› 2023, Vol. 49 ›› Issue (6): 1662-1668.doi: 10.13481/j.1671-587X.20230635
收稿日期:2022-08-08
出版日期:2023-11-28
发布日期:2023-12-22
通讯作者:
刘敏
E-mail:liu_min99@jlu.edu.cn
作者简介:郭晶莹(1998-),女,内蒙古自治区巴彦淖尔市人,在读硕士研究生,主要从事牙周疾病基础和临床方面的研究 。
基金资助:
Received:2022-08-08
Online:2023-11-28
Published:2023-12-22
摘要:
转化生长因子β(TGF-β)是一种多功能生长因子,既参与调控细胞增殖分化和基因表达,也是组织修复和纤维化反应中的中枢效应因子,在纤维化疾病的发生发展中发挥重要作用。TGF-β通常以潜伏复合物的形式分泌并储存于细胞外基质(ECM)中,被激活后通过经典的Smad通路和丝裂原活化蛋白激酶(MAPK)等非Smad通路发挥作用。在遗传性牙龈纤维瘤、药物性牙龈增生和口腔黏膜下纤维化等口腔软组织纤维化疾病中,TGF-β被激活且高表达,其在通过刺激Ⅰ型胶原增生、诱导肌成纤维细胞分化和促进细胞外基质(ECM)合成的同时抑制ECM降解,使ECM过度沉积进而导致纤维化。现结合近年来国内外相关研究,分析TGF-β活化及信号传导功能,并对其在遗传性牙龈纤维瘤、药物性牙龈增生和口腔黏膜下纤维化发生发展中的影响进行阐述,旨在为口腔软组织纤维化疾病的机制研究和精准治疗提供新的思路和方向。
中图分类号:
郭晶莹,潘启源,李芳,熊曼雯,王若琳,刘敏. 转化生长因子β对口腔软组织纤维化疾病发生发展影响的研究进展[J]. 吉林大学学报(医学版), 2023, 49(6): 1662-1668.
| 1 | BIERNACKA A, DOBACZEWSKI M, FRANGOGIANNIS N G. TGF-β signaling in fibrosis[J]. Growth Factors, 2011, 29(5): 196-202. |
| 2 | LODYGA M, HINZ B. TGF-β1 - A truly transforming growth factor in fibrosis and immunity[J]. Semin Cell Dev Biol, 2020, 101: 123-139. |
| 3 | COLETTA R D, GRANER E. Hereditary gingival fibromatosis: a systematic review[J]. J Periodontol, 2006, 77(5): 753-764. |
| 4 | FU M M, CHIN Y T, FU E, et al. Role of transforming growth factor-beta1 in cyclosporine-induced epithelial-to-mesenchymal transition in gingival epithelium[J]. J Periodontol, 2015, 86(1): 120-128. |
| 5 | SHIH Y H, WANG T H, SHIEH T M, et al. Oral submucous fibrosis:a review on etiopathogenesis, diagnosis,and therapy[J].Int J Mol Sci, 2019,20(12):2940. |
| 6 | HU H H, CHEN D Q, WANG Y N, et al. New insights into TGF-β/Smad signaling in tissue fibrosis[J]. Chem Biol Interact, 2018, 292: 76-83. |
| 7 | 侯梅娟, 赵 斌, 林崇韬. 遗传性牙龈纤维瘤病发病机制研究进展[J]. 口腔医学研究, 2012, 28(1): 90-92. |
| 8 | MORIKAWA M, DERYNCK R, MIYAZONO K. TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology[J]. Cold Spring Harb Perspect Biol, 2016, 8(5): a021873. |
| 9 | MURPHY-ULLRICH J E, SUTO M J. Thrombospondin-1 regulation of latent TGF-β activation: a therapeutic target for fibrotic disease[J]. Matrix Biol, 2018, 68/69: 28-43. |
| 10 | BUDI E H, SCHAUB J R, DECARIS M, et al.TGF-β as a driver of fibrosis: physiological roles and therapeutic opportunities[J]. J Pathol, 2021, 254(4): 358-373. |
| 11 | FRANGOGIANNIS N. Transforming growth factor-β in tissue fibrosis[J].J Exp Med,2020,217(3):e20190103. |
| 12 | DERYNCK R, BUDI E H. Specificity, versatility, and control of TGF-β family signaling[J]. Sci Signal, 2019, 12(570): eaav5183. |
| 13 | ROBERTS A B, SPORN M B, ASSOIAN R K, et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro [J].Proc Natl Acad Sci U S A, 1986, 83(12): 4167-4171. |
| 14 | WRIGHT H J, CHAPPLE I L, MATTHEWS J B. TGF-beta isoforms and TGF-beta receptors in drug-induced and hereditary gingival overgrowth[J]. J Oral Pathol Med, 2001, 30(5): 281-289. |
| 15 | PITIYAGE G N, LIM K P, GEMENITZIDIS E,et al. Increased secretion of tissue inhibitors of metalloproteinases 1 and 2 (TIMPs-1 and-2) in fibroblasts are early indicators of oral sub-mucous fibrosis and ageing[J].J Oral Pathol Med,2012,41(6): 454-462. |
| 16 | HART T C, ZHANG Y Z, GORRY M C, et al. A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1[J]. Am J Hum Genet, 2002,70(4): 943-954. |
| 17 | HÄKKINEN L, CSISZAR A. Hereditary gingival fibromatosis: characteristics and novel putative pathogenic mechanisms[J]. J Dent Res, 2007, 86(1): 25-34. |
| 18 | TIPTON D A, DABBOUS M K. Autocrine transforming growth factor beta stimulation of extracellular matrix production by fibroblasts from fibrotic human gingiva[J]. J Periodontol, 1998, 69(6): 609-619. |
| 19 | GAO Q, YANG C C, MENG L Y, et al. Activated KCNQ1 channel promotes fibrogenic response in hereditary gingival fibromatosis via clustering and activation of Ras[J].J Periodontal Res,2021,56(3):471-481. |
| 20 | MARTELLI-JUNIOR H, COTRIM P, GRANER E, et al. Effect of transforming growth factor-beta1, interleukin-6, and interferon-gamma on the expression of type I collagen, heat shock protein 47, matrix metalloproteinase (MMP)-1 and MMP-2 by fibroblasts from normal gingiva and hereditary gingival fibromatosis[J]. J Periodontol, 2003, 74(3): 296-306. |
| 21 | GAWRON K, OCHAŁA-KŁOS A, NOWAKOWSKA Z, et al. TIMP-1 association with collagen type I overproduction in hereditary gingival fibromatosis[J]. Oral Dis, 2018, 24(8): 1581-1590. |
| 22 | SELVARAJAH B, AZUELOS I, PLATÉ M, et al. mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β1-induced collagen biosynthesis[J]. Sci Signal, 2019, 12(582): eaav3048. |
| 23 | BITU C C, SOBRAL L M, KELLERMANN M G,et al.Heterogeneous presence of myofibroblasts in hereditary gingival fibromatosis[J].J Clin Periodontol,2006,33(6): 393-400. |
| 24 | SMITH P C, CÁCERES M, MARTINEZ J. Induction of the myofibroblastic phenotype in human gingival fibroblasts by transforming growth factor-beta1: role of RhoA-ROCK and c-Jun N-terminal kinase signaling pathways[J]. J Periodontal Res, 2006, 41(5): 418-425. |
| 25 | SOBRAL L M, MONTAN P F, MARTELLI-JUNIOR H, et al. Opposite effects of TGF-beta1 and IFN-gamma on transdifferentiation of myofibroblast in human gingival cell cultures[J]. J Clin Periodontol, 2007, 34(5): 397-406. |
| 26 | SOBRAL L M, MONTAN P F, ZECCHIN K G,et al. Smad7 blocks transforming growth factor-β1-induced gingival fibroblast-myofibroblast transition via inhibitory regulation of Smad2 and connective tissue growth factor[J]. J Periodontol, 2011, 82(4): 642-651. |
| 27 | LEIVONEN S K, HÄKKINEN L, LIU D, et al. Smad3 and extracellular signal-regulated kinase 1/2 coordinately mediate transforming growth factor-beta-induced expression of connective tissue growth factor in human fibroblasts[J]. J Invest Dermatol, 2005,124(6): 1162-1169. |
| 28 | BLACK S A Jr, TRACKMAN P C. Transforming growth factor-beta1 (TGFbeta1) stimulates connective tissue growth factor (CCN2/CTGF) expression in human gingival fibroblasts through a RhoA-independent, Rac1/Cdc42-dependent mechanism: statins with forskolin block TGFbeta1-induced CCN2/CTGF expression[J].J Biol Chem, 2008,283(16):10835-10847. |
| 29 | VESCARELLI E, PILLONI A, DOMINICI F, et al. Autophagy activation is required for myofibroblast differentiation during healing of oral mucosa[J]. J Clin Periodontol, 2017, 44(10): 1039-1050. |
| 30 | DE ANDRADE C R, COTRIN P, GRANER E, et al. Transforming growth factor-beta1 autocrine stimulation regulates fibroblast proliferation in hereditary gingival fibromatosis[J].J Periodontol, 2001,72(12):1726-1733. |
| 31 | JOHNSON B D, EL-GUINDY M, AMMONS W F, et al. A defect in fibroblasts from an unidentified syndrome with gingival hyperplasia as the predominant feature[J]. J Periodontal Res, 1986, 21(4): 403-413. |
| 32 | HASSELL T M, ROEBUCK S, PAGE R C, et al. Quantitative histopathologic assessment of developing phenytoin-induced gingival overgrowth in the cat[J]. J Clin Periodontol, 1982, 9(5): 365-372. |
| 33 | SUBRAMANI T, RATHNAVELU V, ALITHEEN N B. The possible potential therapeutic targets for drug induced gingival overgrowth[J]. Mediators Inflamm, 2013, 2013: 639468. |
| 34 | COTRIM P, DE ANDRADE C R, MARTELLI-JUNIOR H, et al. Expression of matrix metalloproteinases in cyclosporin-treated gingival fibroblasts is regulated by transforming growth factor (TGF)-beta1 autocrine stimulation[J]. J Periodontol, 2002, 73(11): 1313-1322. |
| 35 | CHIN Y T, TU H P, LIN C Y, et al. Antioxidants protect against gingival overgrowth induced by cyclosporine A[J].J Periodontal Res, 2021,56(2):397-407. |
| 36 | UZEL M I, KANTARCI A, HONG H H, et al. Connective tissue growth factor in drug-induced gingival overgrowth[J]. J Periodontol, 2001, 72(7): 921-931. |
| 37 | KANTARCI A, BLACK S A, XYDAS C E, et al. Epithelial and connective tissue cell CTGF/CCN2 expression in gingival fibrosis[J].J Pathol,2006,210(1): 59-66. |
| 38 | TRACKMAN P C, KANTARCI A. Molecular and clinical aspects of drug-induced gingival overgrowth[J]. J Dent Res, 2015, 94(4): 540-546. |
| 39 | KANTARCI A, AUGUSTIN P, FIRATLI E, et al. Apoptosis in gingival overgrowth tissues[J]. J Dent Res, 2007, 86(9): 888-892. |
| 40 | KANTARCI A, NSEIR Z, KIM Y S, et al. Loss of basement membrane integrity in human gingival overgrowth[J]. J Dent Res, 2011, 90(7): 887-893. |
| 41 | SUME S S, BERKER E, ILARSLAN Y, et al. Elevated interleukin-17A expression in amlodipine-induced gingival overgrowth[J]. J Periodontal Res, 2020, 55(5): 613-621. |
| 42 | SUBRAMANI T, RATHNAVELU V, YEAP S K, et al. Influence of mast cells in drug-induced gingival overgrowth[J]. Mediators Inflamm, 2013, 2013: 275172. |
| 43 | ARTUC M, STECKELINGS U M, HENZ B M. Mast cell-fibroblast interactions: human mast cells as source and inducers of fibroblast and epithelial growth factors[J]. J Invest Dermatol, 2002, 118(3): 391-395. |
| 44 | MARTIN M M, BUCKENBERGER J A, JIANG J M, et al. TGF-beta1 stimulates human AT1 receptor expression in lung fibroblasts by cross talk between the Smad, p38 MAPK, JNK, and PI3K signaling pathways[J]. Am J Physiol Lung Cell Mol Physiol, 2007, 293(3): L790-L799. |
| 45 | SHEN Y W, SHIH Y H, FUH L J, et al. Oral submucous fibrosis: a review on biomarkers, pathogenic mechanisms,and treatments[J].Int J Mol Sci,2020,21(19): 7231. |
| 46 | KHAN I, KUMAR N, PANT I, et al. Activation of TGF-β pathway by areca nut constituents: a possible cause of oral submucous fibrosis[J]. PLoS One, 2012, 7(12): e51806. |
| 47 | MOUTASIM K A, JENEI V, SAPIENZA K, et al. Betel-derived alkaloid up-regulates keratinocyte alphavbeta6 integrin expression and promotes oral submucous fibrosis[J]. J Pathol,2011,223(3): 366-377. |
| 48 | HSIEH Y P, WU K J, CHEN H M, et al. Arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts: suppression by epigallocatechin-3-gallate[J]. J Formos Med Assoc, 2018, 117(6): 527-534. |
| 49 | CHANG J Z, YANG W H, DENG Y T, et al. EGCG blocks TGFβ1-induced CCN2 by suppressing JNK and p38 in buccal fibroblasts[J].Clin Oral Investig, 2013, 17(2): 455-461. |
| 50 | PANT I, KUMAR N, KHAN I, et al. Role of areca nut induced TGF-β and epithelial-mesenchymal interaction in the pathogenesis of oral submucous fibrosis[J]. PLoS One, 2015, 10(6): e0129252. |
| [1] | 李舒,郭迦期,李宛凇,甄艳凤,翟红佳,李捷,房辉. 芬戈莫德对2型糖尿病小鼠肝纤维化的改善作用及其机制[J]. 吉林大学学报(医学版), 2026, 52(2): 330-339. |
| [2] | 林潇,周梦,林帆,姚秀娟. 特发性肺纤维化组织中脂肪酸代谢相关基因的生物信息学分析及实验验证[J]. 吉林大学学报(医学版), 2026, 52(1): 93-104. |
| [3] | 唐小茜,温升聪,董振亚,陈静仪,曹煜,张云华. 工程化外泌体递送ANGPTL6 mRNA对小鼠肝纤维化的改善作用[J]. 吉林大学学报(医学版), 2025, 51(6): 1452-1463. |
| [4] | 滕欢欢,孙光,姜锐,孙立伟,刘建增. 生肌玉红膏提取物对斑马鱼皮肤创面愈合的促进作用及其机制[J]. 吉林大学学报(医学版), 2025, 51(5): 1221-1229. |
| [5] | 岳星,李雪梅,张寒潇,左川弋,朱莉娟,吕菁,张承舜,曹新. 血清总胆汁酸水平在ApoE-/-小鼠心律失常发生中的作用[J]. 吉林大学学报(医学版), 2025, 51(4): 879-886. |
| [6] | 许惠仙,徐慧,全吉淑,郑峰. 草苁蓉环烯醚萜苷对大鼠肝脏癌前病变的抑制作用及其机制[J]. 吉林大学学报(医学版), 2025, 51(4): 887-895. |
| [7] | 龙光文,张谦,杨秀林,孙鸿鹏,吉春玲. 抑制miR-193a-5p表达对急性呼吸窘迫综合征大鼠肺纤维化的改善作用及其机制[J]. 吉林大学学报(医学版), 2024, 50(6): 1491-1498. |
| [8] | 王飞娜,米旭光,林秀英,付建华,刘磊,于歆悦,臧欢欢,刘霖君,陈士玲,方艳秋. Wnt/β-catenin信号通路抑制剂MSAB对人子宫内膜基质细胞纤维化反应的影响[J]. 吉林大学学报(医学版), 2024, 50(5): 1266-1274. |
| [9] | 魏俊萍,符达佳,孟庆雯,林道飞,林燕仔. 骨髓间充质干细胞来源外泌体对异丙肾上腺素诱导的大鼠心肌纤维化的影响及其作用机制[J]. 吉林大学学报(医学版), 2024, 50(5): 1348-1357. |
| [10] | 廖昭辉,谢正元. 肝纤维化发病的分子机制及其相关治疗靶点的研究进展[J]. 吉林大学学报(医学版), 2024, 50(5): 1450-1456. |
| [11] | 陈潭,陈艳. 巨噬细胞极化调控纤维化机制的研究进展[J]. 吉林大学学报(医学版), 2024, 50(5): 1465-1473. |
| [12] | 阮颖新,贾俊亚,武占飞,商文雅,张鹏宇. NLRP3炎症小体在大鼠单侧输尿管梗阻引起肾间质纤维化中的作用及其机制[J]. 吉林大学学报(医学版), 2024, 50(3): 587-595. |
| [13] | 周佳,邱智东,林喆,律广富,许佳明,林贺,王可欣,王雨辰,黄晓巍. 白屈菜红碱对人卵巢癌SKOV3细胞迁移、侵袭和上皮-间质转化的影响[J]. 吉林大学学报(医学版), 2024, 50(1): 25-32. |
| [14] | 何涛,李振江,丁炳谦. 川芎嗪对胶质瘤干细胞裸鼠皮下移植瘤生长、TGF-β信号通路和上皮-间质转化的影响[J]. 吉林大学学报(医学版), 2023, 49(6): 1437-1444. |
| [15] | 刘星,刘佳丽,聂连桂,刘茂军,赵俊雄,汪刘洋,杨军. 二氧化硫对大鼠急性心肌缺血损伤后心肌纤维化的改善作用及其机制[J]. 吉林大学学报(医学版), 2023, 49(5): 1125-1133. |
|
