| 12 | 0 | 38 |
| 下载次数 | 被引频次 | 阅读次数 |
目的:探索骨形态发生蛋白(bone morphogenetic protein, BMP)信号通过成纤维细胞生长因子20(fibroblast growth factor 20, FGF20)对多疣壁虎断尾再生的作用机制。方法:构建多疣壁虎断尾再生模型,采用免疫荧光组织化学方法检测BMP信号在12 d再生组织中的表达情况。断尾后隔天腹腔注射BMP信号抑制剂,在第12天观察断尾再生情况,并采用免疫荧光组织化学方法检测FGF20的表达。在体外培养芽基细胞中加入BMP激动剂,采用免疫荧光细胞化学方法检测FGF20表达变化。通过双荧光素酶报告基因和染色质免疫沉淀实验检测SMAD1/5/9对FGF20的转录调控作用。结果:断尾后12 d,BMP4/7和BMPR1A在愈伤上皮和芽基细胞中均有表达,阻碍BMP信号显著抑制尾巴再生以及FGF20的表达。体外培养芽基细胞中激活BMP信号可上调FGF20的表达。SMAD1对FGF20起到正转录调控作用。结论:BMP信号通过SMAD1正转录调控FGF20的表达,进而参与调控多疣壁虎的尾巴再生。
Abstract:Objective: To explore the mechanism by which bone morphogenetic protein(BMP) signaling regulates fibroblast growth factor 20(FGF20) during tail regeneration in Gekko japonicus. Methods: A tail regeneration model was established in Gekko japonicus. Immunofluorescence histochemistry was used to detect the expression of BMP signaling in the regenerating tissue on days 12. After tail amputation, BMP signaling inhibitors were injected intraperitoneally every other day and the regenerating was then evaluated on days 12. The expression of FGF20 was then detected by immunofluorescence histochemistry. In vitro cultured blastemal cells were treated with BMP agonists and immunofluorescence cytochemistry was used to detect FGF20 expression. Dual luciferase reporter system and chromatin immunoprecipitation assay were used to analyze the transcriptional regulation of FGF20 by SMAD1/5/9. Results: BMP4/7 and BMPR1A were expressed in the regeneration tissue on days 12 after tail amputation. Inhibition of BMP signaling significantly inhibited tail regeneration and the expression of FGF20. In vitro, activation of BMP signaling in cultured blastemal cells led to an upregulation of FGF20 expression. SMAD1 positively regulated the transcription of FGF20. Conclusion: BMP signaling positively regulates the transcription of FGF20 through SMAD1, thereby regulating tail regeneration in Gekko japonicus.
[1]Alibardi L. Regeneration among animals:an evolutionary hypothesis related to aquatic versus terrestrial environment[J].Dev Biol, 2023, 501:74-80.
[2]Sánchez M, Ceci M L, Gutiérrez D, et al. Mechanosensory organ regeneration in zebrafish depends on a population of multipotent progenitor cells kept latent by Schwann cells[J].BMC Biol, 2016, 14:27.
[3]Huang L, Ho C, Ye X, et al. Mechanisms and translational applications of regeneration in limbs:From renewable animals to humans[J]. Anat Anz, 2024, 255:152288.
[4]Okamura D M, Nguyen E D, Collins S J, et al. Mammalian organ regeneration in spiny mice[J]. J Muscle Res Cell Motil,2023, 44(2):39-52.
[5]Daponte V, Tylzanowski P, Forlino A. Appendage regeneration in vertebrates:what makes this possible?[J]. Cells, 2021,10(2):242.
[6]Liu Y, Zhou Q, Wang Y, et al. Gekko japonicus genome reveals evolution of adhesive toe pads and tail regeneration[J].Nat Commun, 2015, 6:10033.
[7]Liu Z, Huang S, Xu M, et al. The vascularization, innervation and myogenesis of early regenerated tail in Gekko japonicus[J]. J Mol Histol, 2021, 52(6):1189-1204.
[8]Farooq M, Khan A W, Kim M S, et al. The role of fibroblast growth factor(FGF)signaling in tissue repair and regeneration[J]. Cells, 2021, 10(11):3242.
[9]Chen K, Rao Z, Dong S, et al. Roles of the fibroblast growth factor signal transduction system in tissue injury repair[J]. Burns Trauma, 2022, 10:tkac005.
[10]Saito N, Nishimura K, Makanae A, et al. Fgf-and Bmpsignaling regulate gill regeneration in ambystoma mexicanum[J]. Dev Biol, 2019, 452(2):104-113.
[11]Vasudevarao M D, Posadas Pena D, Ihle M, et al. BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress[J]. Nat Commun, 2025, 16(1):1708.
[12]Li X, Xie R, Luo Y, et al. Cooperation of TGF-β and FGF signalling pathways in skin development[J]. Cell Prolif,2023, 56(11):e13489.
[13]Haerlingen B, Opitz R, Vandernoot I, et al. Mesodermal FGF and BMP govern the sequential stages of zebrafish thyroid specification[J]. Development, 2023, 150(10):dev201023.
[14]Storer M A, Miller F D. Cellular and molecular mechanisms that regulate mammalian digit tip regeneration[J]. Open Biol,2020, 10(9):200194.
[15]Schliermann A, Nickel J. Unraveling the connection between fibroblast growth factor and bone morphogenetic protein signaling[J]. Int J Mol Sci, 2018, 19(10):3220.
[16]Makanae A, Mitogawa K, Satoh A. Cooperative inputs of Bmp and Fgf signaling induce tail regeneration in urodele amphibians[J]. Dev Biol, 2016, 410(1):45-55.
[17]Zhu X J, Liu Y, Dai Z M, et al. BMP-FGF signaling axis mediates Wnt-induced epidermal stratification in developing mammalian skin[J]. PLoS Genet, 2014, 10(10):e1004687.
[18]Thompson J D, Ou J H, Lee N, et al. Identification and requirements of enhancers that direct gene expression during zebrafish fin regeneration[J]. Development, 2020, 147(14):dev191262.
[19]Ho W K W, Freem L, Zhao D, et al. Feather arrays are patterned by interacting signalling and cell density waves[J].PLoS Biol, 2019, 17(2):e3000132.
[20]Li Z, Li M X, Huang S, et al. The expression pattern of Wnt6, Wnt10A, and HOXA13 during regenerating tails of Gekko Japonicus[J]. Gene Expr Patterns, 2024, 53:119374.
[21]Franco R A G, McKenna E, Robey P G, et al. Inhibition of BMP signaling with LDN 193189 can influence bone marrow stromal cell fate but does not prevent hypertrophy during chondrogenesis[J]. Stem Cell Rep, 2022, 17(3):616-632.
[22]Malinauskas T, Moore G, Rudolf A F, et al. Molecular mechanism of BMP signal control by Twisted gastrulation[J]. Nat Commun, 2024, 15(1):4976.
[23]Glotzer G L, Tardivo P, Tanaka E M. Canonical Wnt signaling and the regulation of divergent mesenchymal Fgf8expression in axolotl limb development and regeneration[J].eLife, 2022, 11:e79762.
[24]Xu M, Wang T, Li W, et al. PGE2 facilitates tail regeneration via activation of Wnt signaling in Gekko japonicus[J].J Mol Histol, 2019, 50(6):551-562.
[25]Vincent E, Villiard E, Sader F, et al. BMP signaling is essential for sustaining proximo-distal progression in regenerating axolotl limbs[J]. Development, 2020, 147(14):dev170829.
[26]von Saucken V E, Windner S E, Armetta G, et al. Postsynaptic BMP signaling regulates myonuclear properties in drosophila larval muscles[J]. J Cell Biol, 2025, 224(1):e202404052.
[27]Liang Y, Rathnayake D, Huang S, et al. BMP signaling is required for amphioxus tail regeneration[J]. Development,2019, 146(4):dev166017.
[28]Sugiura N, Agata K. FGF-stimulated tendon cells embrace a chondrogenic fate with BMP7 in newt tissue culture[J].Dev Growth Differ, 2024, 66(3):182-193.
基本信息:
DOI:10.16424/j.cnki.cn32-1807/r.2026.02.001
中图分类号:R-332
引用信息:
[1]赵彧,徐嫣然,王引,等.BMP信号上调FGF20促进多疣壁虎断尾再生[J].南通大学学报(医学版),2026,46(02):105-110.DOI:10.16424/j.cnki.cn32-1807/r.2026.02.001.
基金信息:
国家自然科学基金资助项目(32100380); 大学生创新创业训练计划项目(S202510304171)
2026-03-15
2026-03-15