The research progress of hypoxia-induced exosomes in the development of associated diseases and the prospects of application in stomatology

doi:10.3877/cma.j.issn.1674-1366.2021.04.009

Abstract

Abstract:

As a crucial role in the progression of lots of diseases, Exosomes are important in participate in intercellular communication. Hypoxia, an important feature of inflammation, ischemic injury and tumor microenvironment, has been proved to increase the production and alter the content of exosomes. Hypoxia may modulate the functions and behavior of recipient cells via this mechanism. The purpose of the article is to review the current information on hypoxia-induced exosomes in the development of associated diseases and the prospects of application in stomatology.

Key words: Hypoxia, Exosomes, MicroRNAs, Ischemic diseases, Tumor microenvironment, Neurological diseases

Yi Li, Beichen Chen, Li Zhu, Xunning Cao, Yihong Duan, Yuhao Luo, Yan Wang. The research progress of hypoxia-induced exosomes in the development of associated diseases and the prospects of application in stomatology[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2021, 15(04): 245-254.

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URL: https://zhkqyxyjzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-1366.2021.04.009

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References 77

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内容物分类	细胞	缺氧状态下细胞外泌体主要内容物变化	内容物分泌改变机制	内容物作用	作用发挥机制
miRNA	脐带间充质干细胞	miR-126↑	由HIF-1α介导	促进内皮细胞增殖，血管生成和迁移，促进骨折愈合	SPRED1/Ras/Erk途径^[4]
		miR-21↑		抑制β细胞凋亡	减轻ER应激、抑制p38 MAPK磷酸化^[11]
	骨髓间充质	miR-216a-5p↑	由HIF-1α介导	调节小胶质细胞M1/M2极化	TLR4/NF-κB/PI3K/AKT途径^[5]
	干细胞	miR-210↑		抑制细胞凋亡	下调ephrin A3、CASP8AP2^[10]
				促进血管生成	上调VEGF^[12]
		miR-125b-5p↑		抑制细胞凋亡	抑制p53基因和BAK1^[12]
		miR-486-5p↑		抑制受损心肌细胞的凋亡	抑制PTEN表达，激活PI3K/AKT信号通路^[13]
		miR-214↑		调节心脏祖细胞的氧化损伤	降低CaMKⅡ^[14]
		miR-149↑		保护心肌细胞	Let-7c/FASLG途径^[15]
	脂肪干细胞	miR-146a↑	由HIF-1α介导	减轻AMI引起的心肌损伤	下调EGR1
		miR-126↑		减少心肌细胞凋亡	减少炎症因子表达^[16]
	心脏祖细胞	miR-15b、miR-17、miR-20a、miR-103、miR-199a、miR-210、miR-292↑	由HIF-1α介导	促进血管生成	未明^[17,18]
				抗心肌纤维化
				减小心肌梗死面积
	心肌细胞	miR-30a↑	由HIF-1α介导	维持心肌细胞自噬	上调beclin-1、Atg12、LC3Ⅱ/LC3Ⅰ^[19]
		miR-152-3p↑		抑制细胞凋亡	Atg12/Bcl-2途径^[20]
		let-7i-5p↑		抑制细胞凋亡	抑制FASLG^[20]
		circHIPK3↑		调节细胞的氧化损伤	miR-29a/IGF-1途径^[21]
	肾小管上皮细胞	miR-23a↑	由HIF-1α介导	激活巨噬细胞促炎极化，增加炎症细胞浸润，促进炎症发生	抑制泛素编辑酶A20，诱发巨噬细胞代谢重编程^[22]
		miR-20a-5p↑		促进细胞增殖、稳定线粒体功能	增加mtDNA的拷贝数^[23]
蛋白质	内皮细胞	LOXL2	由HIF-1α介导	参与纤维化、伤口愈合过程	调节ECM重塑^[24]
	肺动脉内皮细胞	15-LO2↑	由HIF-1α介导	促进细胞迁移改善肺动脉高压	STAT3通路^[25]

内容物分类	细胞	缺氧状态下细胞外泌体主要内容物变化	内容物分泌改变机制	内容物作用	作用发挥机制
miRNA	脐带间充质干细胞	miR-126↑	由HIF-1α介导	促进内皮细胞增殖，血管生成和迁移，促进骨折愈合	SPRED1/Ras/Erk途径^[4]
		miR-21↑		抑制β细胞凋亡	减轻ER应激、抑制p38 MAPK磷酸化^[11]
	骨髓间充质	miR-216a-5p↑	由HIF-1α介导	调节小胶质细胞M1/M2极化	TLR4/NF-κB/PI3K/AKT途径^[5]
	干细胞	miR-210↑		抑制细胞凋亡	下调ephrin A3、CASP8AP2^[10]
				促进血管生成	上调VEGF^[12]
		miR-125b-5p↑		抑制细胞凋亡	抑制p53基因和BAK1^[12]
		miR-486-5p↑		抑制受损心肌细胞的凋亡	抑制PTEN表达，激活PI3K/AKT信号通路^[13]
		miR-214↑		调节心脏祖细胞的氧化损伤	降低CaMKⅡ^[14]
		miR-149↑		保护心肌细胞	Let-7c/FASLG途径^[15]
	脂肪干细胞	miR-146a↑	由HIF-1α介导	减轻AMI引起的心肌损伤	下调EGR1
		miR-126↑		减少心肌细胞凋亡	减少炎症因子表达^[16]
	心脏祖细胞	miR-15b、miR-17、miR-20a、miR-103、miR-199a、miR-210、miR-292↑	由HIF-1α介导	促进血管生成	未明^[17,18]
				抗心肌纤维化
				减小心肌梗死面积
	心肌细胞	miR-30a↑	由HIF-1α介导	维持心肌细胞自噬	上调beclin-1、Atg12、LC3Ⅱ/LC3Ⅰ^[19]
		miR-152-3p↑		抑制细胞凋亡	Atg12/Bcl-2途径^[20]
		let-7i-5p↑		抑制细胞凋亡	抑制FASLG^[20]
		circHIPK3↑		调节细胞的氧化损伤	miR-29a/IGF-1途径^[21]
	肾小管上皮细胞	miR-23a↑	由HIF-1α介导	激活巨噬细胞促炎极化，增加炎症细胞浸润，促进炎症发生	抑制泛素编辑酶A20，诱发巨噬细胞代谢重编程^[22]
		miR-20a-5p↑		促进细胞增殖、稳定线粒体功能	增加mtDNA的拷贝数^[23]
蛋白质	内皮细胞	LOXL2	由HIF-1α介导	参与纤维化、伤口愈合过程	调节ECM重塑^[24]
	肺动脉内皮细胞	15-LO2↑	由HIF-1α介导	促进细胞迁移改善肺动脉高压	STAT3通路^[25]

癌症	细胞系	缺氧状态下细胞外泌体主要内容物变化	内容物作用	作用发挥机制
胶质母细胞瘤	U87MG、U251	特异性表达miR-301a	降低辐射敏感性	抑制TCEAL7^[49]
		miR-1246↑	促进肿瘤细胞增殖	抑制TERF2IP，促进巨噬细胞M2极化^[50]
			促进肿瘤细胞迁移	抑制TERF2IP，促进巨噬细胞M2极化^[50]
		LncRNA 01060↑	促进肿瘤细胞增殖	MZF1/c-Myc/HIF1α途径^[51]
			促进肿瘤细胞迁移	MZF1/c-Myc/HIF1α途径^[51]
肺癌	NCI-H1437，-H1648，-H1792，-H2087	miR-23a↑	促进血管生成	PHD1/2/HIF-1α/VEGF^[52]
	NCI-H1437，-H1648，-H1792，-H2087		促进肿瘤细胞迁移	抑制ZO-1^[52]
	NCI-H1437，-H1792，-H2087	miR-103a↑	调节免疫反应	PTEN途径，促进巨噬细胞M2极化^[53]
			促进血管生成	PTEN途径，促进巨噬细胞M2极化^[53]
			促进肿瘤细胞增殖	PTEN途径，促进巨噬细胞M2极化^[53]
			促进肿瘤细胞迁移	PTEN途径，促进巨噬细胞M2极化^[53]
	A549、H1299、PC9	PKM2↑	增加肿瘤耐药性	PKM2/BCL2途径^[54]
	IGR-Heu	TGF-β↑	调节免疫反应	降低NKG2D表达^[55]
口腔鳞状细胞癌	SCC-9、CAL-27	miR-21↑	促进肿瘤细胞迁移	诱导EMT^[56]
口腔鳞状细胞癌			调节免疫反应	通过PTEN/PD-L1途径增强MDSC对γδT细胞的抑制作用^[57]
结直肠癌	HT29、HCT116	Wnt4 mRNA↑	促进肿瘤细胞迁移	Wnt/β-catenin途径^[58]
	HCT116、SW480	circ-133↑	促进肿瘤细胞迁移	GEF-H1/RhoA途径^[59]
	DLD-1、HT29	miR-410-3p↑	促进肿瘤细胞迁移	PTEN/PI3K/Akt途径^[60]
肝细胞癌	Hep G2	miR-23a↑	促进血管生成	激活SIRT1^[61]
	Huh7、MHCC-97H	miR-1273f↑	促进肿瘤细胞增殖	Wnt/β-catenin途径^[62]
			促进肿瘤细胞迁移	Wnt/β-catenin途径^[62]
胰腺癌	PANC-1、MIA PaCa-2、	lncRNA UCA1↑	促进血管生成	miR-96-5p/AMOTL2/ERK1/2途径^[63]
	BxPC-3、Aspc-1、Sw1990		促进肿瘤细胞增殖	抑制miR-135a^[64]
	PANC-1、BxPC-3	miR-301a-3p↑	调节免疫反应	PTEN途径，促进巨噬细胞M2极化^[65]
			促进血管生成	PTEN途径，促进巨噬细胞M2极化^[65]
			促进肿瘤细胞增殖	PTEN途径，促进巨噬细胞M2极化^[65]
			促进肿瘤细胞迁移	PTEN途径，促进巨噬细胞M2极化^[65]
肾癌	Caki-1、KMRC-1	CA9↑	促进血管生成	上调内皮细胞MMP2表达^[66]
			促进肿瘤细胞迁移	未明
膀胱癌	5637、UMUC2、T24	lncRNA UCA1↑	促进肿瘤细胞迁移	miR-145/ZEB1/2/FSCN1途径，诱导EMT^[67,68]
宫颈癌	Siha、Caski、C33a、MS751、ME180	miR-221-3p↑	促进肿瘤细胞迁移	下调VASH1，激活AKT、ERK途径^[69]
前列腺癌	PC3	MMP-9↑	促进肿瘤细胞迁移	降解ECM^[70]

癌症	细胞系	缺氧状态下细胞外泌体主要内容物变化	内容物作用	作用发挥机制
胶质母细胞瘤	U87MG、U251	特异性表达miR-301a	降低辐射敏感性	抑制TCEAL7^[49]
		miR-1246↑	促进肿瘤细胞增殖	抑制TERF2IP，促进巨噬细胞M2极化^[50]
			促进肿瘤细胞迁移	抑制TERF2IP，促进巨噬细胞M2极化^[50]
		LncRNA 01060↑	促进肿瘤细胞增殖	MZF1/c-Myc/HIF1α途径^[51]
			促进肿瘤细胞迁移	MZF1/c-Myc/HIF1α途径^[51]
肺癌	NCI-H1437，-H1648，-H1792，-H2087	miR-23a↑	促进血管生成	PHD1/2/HIF-1α/VEGF^[52]
	NCI-H1437，-H1648，-H1792，-H2087		促进肿瘤细胞迁移	抑制ZO-1^[52]
	NCI-H1437，-H1792，-H2087	miR-103a↑	调节免疫反应	PTEN途径，促进巨噬细胞M2极化^[53]
			促进血管生成	PTEN途径，促进巨噬细胞M2极化^[53]
			促进肿瘤细胞增殖	PTEN途径，促进巨噬细胞M2极化^[53]
			促进肿瘤细胞迁移	PTEN途径，促进巨噬细胞M2极化^[53]
	A549、H1299、PC9	PKM2↑	增加肿瘤耐药性	PKM2/BCL2途径^[54]
	IGR-Heu	TGF-β↑	调节免疫反应	降低NKG2D表达^[55]
口腔鳞状细胞癌	SCC-9、CAL-27	miR-21↑	促进肿瘤细胞迁移	诱导EMT^[56]
口腔鳞状细胞癌			调节免疫反应	通过PTEN/PD-L1途径增强MDSC对γδT细胞的抑制作用^[57]
结直肠癌	HT29、HCT116	Wnt4 mRNA↑	促进肿瘤细胞迁移	Wnt/β-catenin途径^[58]
	HCT116、SW480	circ-133↑	促进肿瘤细胞迁移	GEF-H1/RhoA途径^[59]
	DLD-1、HT29	miR-410-3p↑	促进肿瘤细胞迁移	PTEN/PI3K/Akt途径^[60]
肝细胞癌	Hep G2	miR-23a↑	促进血管生成	激活SIRT1^[61]
	Huh7、MHCC-97H	miR-1273f↑	促进肿瘤细胞增殖	Wnt/β-catenin途径^[62]
			促进肿瘤细胞迁移	Wnt/β-catenin途径^[62]
胰腺癌	PANC-1、MIA PaCa-2、	lncRNA UCA1↑	促进血管生成	miR-96-5p/AMOTL2/ERK1/2途径^[63]
	BxPC-3、Aspc-1、Sw1990		促进肿瘤细胞增殖	抑制miR-135a^[64]
	PANC-1、BxPC-3	miR-301a-3p↑	调节免疫反应	PTEN途径，促进巨噬细胞M2极化^[65]
			促进血管生成	PTEN途径，促进巨噬细胞M2极化^[65]
			促进肿瘤细胞增殖	PTEN途径，促进巨噬细胞M2极化^[65]
			促进肿瘤细胞迁移	PTEN途径，促进巨噬细胞M2极化^[65]
肾癌	Caki-1、KMRC-1	CA9↑	促进血管生成	上调内皮细胞MMP2表达^[66]
			促进肿瘤细胞迁移	未明
膀胱癌	5637、UMUC2、T24	lncRNA UCA1↑	促进肿瘤细胞迁移	miR-145/ZEB1/2/FSCN1途径，诱导EMT^[67,68]
宫颈癌	Siha、Caski、C33a、MS751、ME180	miR-221-3p↑	促进肿瘤细胞迁移	下调VASH1，激活AKT、ERK途径^[69]
前列腺癌	PC3	MMP-9↑	促进肿瘤细胞迁移	降解ECM^[70]

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