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{{Infobox_gene}}
'''生長分化因子11'''（{{langx|en|growth differentiation factor 11, GDF11}}），亦稱為'''骨塑型蛋白11'''（{{langx|en|bone morphogenetic protein 11, BMP-11}}），是一種由人體中的生長分化因子11[[基因]]所[[遺傳密碼|編碼]]的[[蛋白質]]。GDF11能形成一種可被骨塑型蛋白1活化的潛伏複合體，進而調節神經生長因子所引發的PC12細胞分化作用<ref name="pmid15988002">{{cite journal | vauthors = Ge G, Hopkins DR, Ho WB, Greenspan DS | title = GDF11 forms a bone morphogenetic protein 1-activated latent complex that can modulate nerve growth factor-induced differentiation of PC12 cells | url = https://archive.org/details/sim_molecular-and-cellular-biology_2005-07_25_14/page/5846 | journal = Molecular and Cellular Biology | volume = 25 | issue = 14 | pages = 5846–5858 | date = July 2005 | pmid = 15988002 | pmc = 1168807 | doi = 10.1128/MCB.25.14.5846-5858.2005 }}</ref>。從分子分類上來看，GDF11隸屬於[[轉化生長因子-β超家族]]<ref name="pmid31681577" />。

GDF11以[[細胞激素]]的形式發揮生物功能，其胺基酸序列在人類、小鼠與大鼠之間呈現高度保守性<ref>{{cite journal | vauthors = Jamaiyar A, Wan W, Janota DM, Enrick MK, Chilian WM, Yin L | title = The versatility and paradox of GDF 11 | journal = Pharmacology & Therapeutics | volume = 175 | pages = 28–34 | date = July 2017 | pmid = 28223232 | pmc = 6319258 | doi = 10.1016/j.pharmthera.2017.02.032 }}</ref>。[[骨塑型蛋白]]類群的共同特徵之一，是其前驅蛋白含有一個多鹼性的蛋白水解處理位點；該位點經切割後，會產生一種含有七個保守[[半胱胺酸]]殘基的成熟蛋白<ref>{{cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=GDF11|title=Gene GDF11|work=Genecards|access-date=2013-05-25}}</ref>。

==組織分布==
GDF11在人體內具有廣泛的組織表現，可在骨骼肌、胰臟、皮膚、腎臟、神經系統及視網膜等多種組織中被偵測到<ref name="pmid31681577">{{cite journal | vauthors = Simoni-Nieves A, Gerardo-Ramírez M, Pedraza-Vázquez G, Chávez-Rodríguez L, Bucio L, Souza V, Miranda-Labra RU, Gomez-Quiroz LE, Gutiérrez-Ruiz MC | title = GDF11 Implications in Cancer Biology and Metabolism. Facts and Controversies | journal = Frontiers in Oncology | volume = 9 | date = 2019 | pmid = 31681577 | pmc = 6803553 | doi = 10.3389/fonc.2019.01039 | doi-access = free }}</ref>。

==對細胞生長與分化的影響==
GDF11隸屬於[[轉化生長因子-β超家族]]，並透過調節[[同源異形基因|Hox基因]]的表現，參與生物體前後軸的發育模式形成<ref name=andersson>{{cite journal | vauthors = Andersson O, Reissmann E, Ibáñez CF | title = Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis | journal = EMBO Reports | volume = 7 | issue = 8 | pages = 831–837 | date = August 2006 | pmid = 16845371 | pmc = 1525155 | doi = 10.1038/sj.embor.7400752 }}</ref>。它能界定Hox基因的表現區域，並在發育中的[[脊髓]][[解剖学方位#相对方位|尾側]]，決定其頭尾向的區域身分<ref name="ReferenceB">{{cite journal | vauthors = Liu JP | title = The function of growth/differentiation factor 11 (Gdf11) in rostrocaudal patterning of the developing spinal cord | journal = Development | volume = 133 | issue = 15 | pages = 2865–2874 | date = August 2006 | pmid = 16790475 | doi = 10.1242/dev.02478 | doi-access = free }}</ref>。

在小鼠發育過程中，GDF11會率先在尾芽與尾側{{le|神經板|Neural plate}}區域表現；若缺失GDF11，則會因前後軸定位的模式形成失調，而導致骨骼結構異常<ref>{{cite journal | vauthors = McPherron AC, Lawler AM, Lee SJ | title = Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11 | journal = Nature Genetics | volume = 22 | issue = 3 | pages = 260–264 | date = July 1999 | pmid = 10391213 | doi = 10.1038/10320 | s2cid = 1172738 }}</ref>。作為一種[[細胞激素]]，GDF11會抑制嗅覺受器神經前驅細胞的增殖，藉此調節{{le|嗅覺上皮|Olfactory epithelium}}中神經元的數量<ref name="ReferenceC">{{cite journal | vauthors = Wu HH, Ivkovic S, Murray RC, Jaramillo S, Lyons KM, Johnson JE, Calof AL | title = Autoregulation of neurogenesis by GDF11 | journal = Neuron | volume = 37 | issue = 2 | pages = 197–207 | date = January 2003 | pmid = 12546816 | doi = 10.1016/S0896-6273(02)01172-8 | s2cid = 15399794 | doi-access = free }}</ref>，並透過控制[[祖細胞|前驅細胞]]的分化時機，進一步調控[[視網膜]]中[[神經節]]細胞的發育數目<ref>{{cite journal | vauthors = Kim J, Wu HH, Lander AD, Lyons KM, Matzuk MM, Calof AL | title = GDF11 controls the timing of progenitor cell competence in developing retina | journal = Science | volume = 308 | issue = 5730 | pages = 1927–1930 | date = June 2005 | pmid = 15976303 | doi = 10.1126/science.1110175 | s2cid = 42002862 | bibcode = 2005Sci...308.1927K | url = https://escholarship.org/uc/item/42r9d2rk}}</ref>。其他小鼠研究亦指出，GDF11可能參與胚胎期的[[中胚層]]形成以及神經生成。

GDF11可與TGF-β超家族的第一型受體[[ACVR1B]]（ALK4）、{{le|轉化生長因子-β受體1|TGF beta receptor 1|TGFBR1}}（ALK5）及{{le|ACVR1C|ACVR1C}}（ALK7）結合，但其訊號傳遞主要是透過ALK4與ALK5進行<ref name=andersson/>。在結構與系統發育層面上，GDF11亦與{{le|肌生成抑制素|myostatin}}密切相關；後者是一種抑制肌肉生長的負向調控因子<ref>{{cite journal | vauthors = McPherron AC, Lee SJ | title = Double muscling in cattle due to mutations in the myostatin gene | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 23 | pages = 12457–12461 | date = November 1997 | pmid = 9356471 | pmc = 24998 | doi = 10.1073/pnas.94.23.12457 | doi-access = free | bibcode = 1997PNAS...9412457M }}</ref><ref>{{cite journal | vauthors = Lee SJ, McPherron AC | title = Myostatin and the control of skeletal muscle mass | journal = Current Opinion in Genetics & Development | volume = 9 | issue = 5 | pages = 604–607 | date = October 1999 | pmid = 10508689 | doi = 10.1016/S0959-437X(99)00004-0 | doi-access = free }}</ref>，相關研究進一步指出，兩者在演化關係上亦具有高度相似性<ref>{{cite journal | vauthors = Kerr T, Roalson EH, Rodgers BD | title = Phylogenetic analysis of the myostatin gene sub-family and the differential expression of a novel member in zebrafish | journal = Evolution & Development | volume = 7 | issue = 5 | pages = 390–400 | date = 2005 | pmid = 16174033 | doi = 10.1111/j.1525-142X.2005.05044.x | bibcode = 2005EvDev...7..390K | s2cid = 6538603 }}</ref>。

儘管GDF11在結構上與{{le|肌生成抑制素|myostatin}}約有90%的相似性，但其作用機制卻與後者相反；GDF11的濃度會隨年齡增長而下降，並在小鼠的骨骼肌中發揮抗老化與促進組織再生的作用<ref>{{cite journal |vauthors=Añón-Hidalgo J, Catalán V, Rodríguez A, Ramírez B, Silva C, Galofré JC, Salvador J, Frühbeck G, Gómez-Ambrosi J |date=March 2019 |title=Circulating GDF11 levels are decreased with age but are unchanged with obesity and type 2 diabetes |journal=Aging |volume=11 |issue=6 |pages=1733–1744 |doi=10.18632/aging.101865 |pmc=6461177 |pmid=30897065}}</ref>。

==人體研究==
人體研究顯示，GDF11濃度會在平均73.71歲時降至零；當內源性GDF11停止產生，幹細胞的DNA修復隨之中止，導致幹細胞死亡並使其族群數量更快速地降至零。由於缺乏造血幹細胞、間質幹細胞等幹細胞將無法存活，這些觀察結果顯示GDF11可能在最大壽命的決定上扮演關鍵角色<ref>{{cite journal | vauthors = Delgado D, Bilbao AM, Beitia M, Garate A, Sánchez P, González-Burguera I, Isasti A, López De Jesús M, Zuazo-Ibarra J, Montilla A, Domercq M, Capetillo-Zarate E, García Del Caño G, Sallés J, Matute C, Sánchez M | title = Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age | journal = International Journal of Molecular Sciences | volume = 22 | issue = 4 | page = 1725 | date = February 2021 | doi = 10.3390/ijms22041725 | pmid = 33572157 | pmc = 7915891 | doi-access = free }}</ref>。

Elevian是一家{{le|大學衍生企業|University spin-off}}，其創辦人包括來自哈佛幹細胞研究所（{{lang|en|Harvard Stem Cell Institute}}）的研究人員──{{le|艾美·威格斯|Amy Wagers}}博士、李・魯賓博士（{{lang|en|Lee Rubin}}）與李・里奇博士（{{lang|en|Rich Lee}}）。該公司已透過兩輪募資，為GDF11研究籌集共計5,800萬美元。2022年6月19日，《[[紐約時報]]》發表了一篇探討GDF11與Elevian的報導，題為''Can a 'Magic' Protein Slow the Aging Process?''<ref name=Zimmerman2022>{{Cite news | vauthors = Zimmerman E |date=2022-07-19 |title=Can a 'Magic' Protein Slow the Aging Process? |language=en-US |work=The New York Times |url=https://www.nytimes.com/2022/07/19/business/aging-protein-elevian.html |access-date=2022-12-05 |issn=0362-4331}}</ref>。報導指出，Elevian計畫自2023年第一季起，展開以GDF11修復人類中風損傷的臨床試驗<ref name=Zimmerman2022/>。

研究指出，身體適能與血清中GDF11濃度呈現相關性，且與先前研究結果相符；該研究顯示，終身從事運動的男性，其血清GDF11水準高於終身久坐的同儕。身體適能不僅會影響GDF11在特定組織中的表現與濃度，也會左右其對運動刺激所引發之調節幅度<ref>{{Cite journal |last1=Schön |first1=Martin |last2=Marček Malenovská |first2=Karin |last3=Nemec |first3=Michal |last4=Alchus Laiferová |first4=Nikoleta |last5=Straka |first5=Igor |last6=Košutzká |first6=Zuzana |last7=Matejička |first7=Peter |last8=Valkovič |first8=Peter |last9=Ukropec |first9=Jozef |last10=Ukropcová |first10=Barbara |date=2023 |title=Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults |journal=Frontiers in Endocrinology |volume=14 |doi=10.3389/fendo.2023.1137048 |doi-access=free |pmid=37033257 |issn=1664-2392|pmc=10073538 }}</ref>。

還有研究指出，重度憂鬱症患者的GDF11濃度顯著低於健康對照組；此外，在老年小鼠中給予GDF11，會藉由刺激神經元自噬來改善記憶，並以不依賴神經新生的方式，緩解老化與類憂鬱症狀<ref>{{Cite journal | vauthors = Moigneu C, Abdellaoui S, Ramos-Brossier M, Pfaffenseller B, Wollenhaupt-Aguiar B, de Azevedo Cardoso T, Chiche A, Kuperwasser N, Azevedo da Silva R, Pedrotti Moreira F, Li H, Oury F, Kapczinski F, Lledo P, Katsimpardi L |date=2023-02-02 |title=Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy |journal=Nature Aging | volume = 3 | issue = 2 |language=en |pages=213–228 |doi=10.1038/s43587-022-00352-3 | pmid = 37118117 |issn=2662-8465|pmc=10154197 }}</ref>。

此外，其他研究還指出，相較於周邊組織，GDF11在胰臟癌組織中的表現量較低，且胰臟癌細胞株亦呈現該生長因子的低度表現。該研究團隊並發現，在一個包含63名胰臟癌患者的研究族群中，GDF11表現量較高者，其存活率顯著優於表現量較低者。這些影響與細胞增殖、遷移及侵襲能力的降低有關，且與先前在肝細胞癌（HCC）與三陰性乳癌（TNBC）中所報告的觀察結果相符。此外，GDF11亦能在胰臟癌細胞株中誘導細胞凋亡<ref name="Simoni-Nieves">{{cite journal | vauthors = Simoni-Nieves A, Gerardo-Ramírez M, Pedraza-Vázquez G, Chávez-Rodríguez L, Bucio L, Souza V, Miranda-Labra RU, Gomez-Quiroz LE, Gutiérrez-Ruiz MC | title = GDF11 Implications in Cancer Biology and Metabolism. Facts and Controversies | journal = Frontiers in Oncology | volume = 9 | date = 2019-10-15 | pmid = 31681577 | pmc = 6803553 | doi = 10.3389/fonc.2019.01039 | doi-access = free }}</ref>。

然而，在130名結直腸癌（CRC）患者的研究中，GDF11在腫瘤組織中的表現量顯著高於正常組織。將患者依GDF11表現量分為低表現與高表現後顯示，高GDF11表現的患者，具有較高比例的淋巴結轉移、較多死亡案例，且存活率較低。

另有研究指出，GDF11的表現量會因多種細胞壓力刺激而上升，包括缺氧與發炎反應；由於腫瘤微環境通常伴隨低氧與發炎狀態，這可能與結腸癌患者中GDF11表現量升高有關<ref name="Simoni-Nieves" />。

==參考資料==
{{reflist}}

==外部連結==
* {{PDBe-KB2|O95390|Growth/differentiation factor 11}}

{{TGF beta signaling}}

GDF11 - 版本历史

imported>InternetArchiveBot：​Add 1 book for verifiability (20260417sim)) #IABot (v2.0.9.5) (GreenC bot

imported>InternetArchiveBot：Add 1 book for verifiability (20260417sim)) #IABot (v2.0.9.5) (GreenC bot