Research progress on the mechanism of miRNA in regulating primary Sjögren's syndrome

doi:10.12092/j.issn.1009-2501.2026.08.010

Abstract

Abstract:

Primary Sj?gren's syndrome (pSS) is a chronic systemic autoimmune disorder whose pathogenesis remains incompletely understood. The current treatment options are limited and there is no curative therapy. microRNA (miRNA), as important post-transcriptional regulatory factors, can widely participate in the pathological processes such as immune dysregulation and tissue damage in pSS, providing new research directions for its diagnosis and treatment. When pSS occurs, the expression of miRNAs in the body will be abnormal. By regulating the expression of miRNAs, it can affect the prognosis and outcome of pSS. Therefore, miRNAs are considered as an important target for anti-pSS treatment. Studies have found that miR-216a-3p, miR-31-5p, etc., can regulate the polarization of macrophages, cell apoptosis, Th17/Treg balance, T/B lymphocytes, glandular function, and type I IFN response through regulating the NF-κB, JAK/STAT, and PI3K/AKT signaling pathways, thereby regulating the occurrence and development of pSS. This article reviews the regulatory mechanisms of miRNAs on pSS, with the aim of providing ideas and basis for the prevention and treatment of pSS.

Key words: miRNA, primary Sj?gren's syndrome, mechanism of action, research progress

CLC Number:

R593.2

Chengzhi WANG, Songwei LI, Yifan LIU, Mengmeng DU, Keying ZHU, Huan LI. Research progress on the mechanism of miRNA in regulating primary Sjögren's syndrome[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(8): 1091-1100.

Figures/Tables 2

References 72

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调节机制	miRNA （表达情况）	动物模型/ 细胞模型/ 临床患者	信号通路	具体调节机制	调控pSS作用	参考文献
调节巨噬细胞极化	miR-31-5p（↑）	SS患者	p38 MAPK	NOS2、IL-1β、TNF-α↓，Arg-1、CD206、IL-10↑；M1极化↓、M2极化↑	炎症浸润、组织损伤、干眼症状↓	[11]
	miR-125b（↓）	SS小鼠	-	CD38↓，CD206↑，M2极化↑；IL-17a、IL-21↓，Th17细胞分化↓	炎症反应↓，唾液腺功能↑	[15]
	miR-100-5p（↑）	干眼症兔	-	NOS2、IRF5↓，CD206、Arg-1、KLF4↑，M2极化↑；CD4⁺Foxp3⁺Tregs↑，Tregs分化↑；TNF-α、IL-1β、IL-6↓	炎症反应、眼干程度↓	[17]
调节细胞凋亡	miR-155-5p（↓）	pSS小鼠、HSGEC细胞	PI3K/AKT	细胞凋亡↓；IL-10、IL-4↑，TNF-α、IL-6↓	炎症反应↓，腺体分泌功能↑	[19]
	miR-155-5p（↓）	SGECs细胞	NF-κB	Bax、caspase 3、caspase 9↓，Bcl-2↑，细胞凋亡↓；TNF-α、IL-6↓	炎症反应、唾液腺损伤↓	[23]
	miR-34a（↓）	NOD小鼠	NF-κB	Bcl-2↑，pro-caspase 9、caspase 9、cleaved-Caspase-3、Cyt C↓，细胞凋亡↓	唾液腺损伤↓	[25]
调节细胞凋亡	miR-223-3p（↓）	SS患者、SEGCs细胞	NF-κB	Bax、caspase-3↓，Bcl-2↑，细胞凋亡↓；IL-6、IL-12、TNF-γ↓	炎症反应↓，泪液分泌↑	[26]
调节细胞凋亡	miR-1207-5p、 miR-4695-3p（↓）	SS患者、HSG细胞	-	Bax、CASP-9、CASP-8↓，Bcl-2↑，细胞凋亡↓	唾液腺功能、唾液分泌↑	[28]
调节Th17/ Treg平衡	miRNA let-7f-5p（-）	NOD/ShiLtJ小鼠	RORC/IL-17A	CD4⁺Foxp3⁺细胞↑、CD4⁺IL-17A⁺细胞↓，Th17/Treg平衡；IL-10、TGF-β↑，IL-6、IL-17A↓	唾液分泌↑、淋巴细胞浸润↓	[31]
	miR-29a-3p（-）	NOD、Balb/c小鼠	miR-29a-3p/T-bet	Th1细胞↓，Th细胞分化↓；CD4⁺T细胞浸润↓，IFN-γ、TNF-α↓	炎症反应↓，免疫微环境、唾液分泌↑	[34]
	miR-23b-3p（↑）	NOD小鼠	NF-κB	TNF-α、IL-6、IL-17A、ING-γ↓，TGF-β1↑，Th1/Th17/Treg平衡	炎症反应↓，唾液分泌↑	[36]
	miR-146a-5p（↑）	SS患者	IL23/IL23R	ADAM17↓，IL-17A、IL-21↑，Th17细胞↑，Th17分化↑	免疫炎症反应↓	[40]
调节T/B 淋巴细胞	miR-216a-3p（-）	pSS大鼠	JAK/STAT	AFF-R、BCR、TLR-9↓，B细胞活化↓； TNF-α、IFN-γ、IL-6↓	炎症反应、组织纤维化↓、唾液分泌↑	[42]
	miR-10a-5p（-）	ESS小鼠	-	Bcl-6↓，B细胞数量、活化↓	唾液腺功能↑	[44]
	miR-125b（-）	SS患者、NOD小鼠	-	PRDM1↓，B细胞活化↓；CD19CD20CD27CD38细胞比例↓	炎症反应、腺体损伤↓，唾液流速、唾液分泌↑	[46]
	hsa-miR-30b-5p （↑）	SS患者	-	B细胞活化↓	炎症浸润↓，腺体功能↑	[48]
	hsa-miR-3202（-）	SS患者	-	MMP2↓，T细胞浸润、增殖侵袭↓	免疫炎症反应、唇腺损伤↓，腺体功能、唾液分泌↑	[49]
	miR-142-3p（↓）	SS患者	-	cAMP生成↓，钙信号↓，蛋白质生成↓；T细胞激活↑	上皮细胞功能、腺体功能↑	[53]
	miR-let-7d-3p（↑）	SS患者	AKT1/mTOR	CD4⁺T比例↓，IL-17↓	炎症反应↓	[57]
	miR-31-5p（↓）	SS患者	-	ECAR、OCR↓，葡萄糖代谢↑， T细胞反应↑	炎症反应↓	[59]
调节腺体功能	ebv-miR-BART13-3p（↓）	SS患者	-	STIM1↑、SOCE↑、钙依赖性基因↑、AQP5↑	腺体功能、唾液分泌↑	[62]
调节Ⅰ型 IFN反应	hsa-miR-145-5p（↑）	SS患者、HSG细胞	-	MUC1、TLR4、I型IFN↓	炎症反应↓，腺体功能↑	[64]
调节Ⅰ型 IFN反应	miR-744-5p（↓）	SS患者	-	PELI3↑，CCL5、CXCL10↓	炎症反应↓	[66]
调节其他机制	hsa-miR-181d-5p（↑）	SS患者	-	TNF-α介导炎症反应↓	腺体损伤↓，唾液分泌↑	[68]
调节其他机制	miR-130a、miR-708（↑）	SS患者	-	MSK1↓，cDC2激活↓，TNF-α、IL-6、 IL-12↓	炎症反应↓	[72]

调节机制	miRNA （表达情况）	动物模型/ 细胞模型/ 临床患者	信号通路	具体调节机制	调控pSS作用	参考文献
调节巨噬细胞极化	miR-31-5p（↑）	SS患者	p38 MAPK	NOS2、IL-1β、TNF-α↓，Arg-1、CD206、IL-10↑；M1极化↓、M2极化↑	炎症浸润、组织损伤、干眼症状↓	[11]
	miR-125b（↓）	SS小鼠	-	CD38↓，CD206↑，M2极化↑；IL-17a、IL-21↓，Th17细胞分化↓	炎症反应↓，唾液腺功能↑	[15]
	miR-100-5p（↑）	干眼症兔	-	NOS2、IRF5↓，CD206、Arg-1、KLF4↑，M2极化↑；CD4⁺Foxp3⁺Tregs↑，Tregs分化↑；TNF-α、IL-1β、IL-6↓	炎症反应、眼干程度↓	[17]
调节细胞凋亡	miR-155-5p（↓）	pSS小鼠、HSGEC细胞	PI3K/AKT	细胞凋亡↓；IL-10、IL-4↑，TNF-α、IL-6↓	炎症反应↓，腺体分泌功能↑	[19]
	miR-155-5p（↓）	SGECs细胞	NF-κB	Bax、caspase 3、caspase 9↓，Bcl-2↑，细胞凋亡↓；TNF-α、IL-6↓	炎症反应、唾液腺损伤↓	[23]
	miR-34a（↓）	NOD小鼠	NF-κB	Bcl-2↑，pro-caspase 9、caspase 9、cleaved-Caspase-3、Cyt C↓，细胞凋亡↓	唾液腺损伤↓	[25]
调节细胞凋亡	miR-223-3p（↓）	SS患者、SEGCs细胞	NF-κB	Bax、caspase-3↓，Bcl-2↑，细胞凋亡↓；IL-6、IL-12、TNF-γ↓	炎症反应↓，泪液分泌↑	[26]
调节细胞凋亡	miR-1207-5p、 miR-4695-3p（↓）	SS患者、HSG细胞	-	Bax、CASP-9、CASP-8↓，Bcl-2↑，细胞凋亡↓	唾液腺功能、唾液分泌↑	[28]
调节Th17/ Treg平衡	miRNA let-7f-5p（-）	NOD/ShiLtJ小鼠	RORC/IL-17A	CD4⁺Foxp3⁺细胞↑、CD4⁺IL-17A⁺细胞↓，Th17/Treg平衡；IL-10、TGF-β↑，IL-6、IL-17A↓	唾液分泌↑、淋巴细胞浸润↓	[31]
	miR-29a-3p（-）	NOD、Balb/c小鼠	miR-29a-3p/T-bet	Th1细胞↓，Th细胞分化↓；CD4⁺T细胞浸润↓，IFN-γ、TNF-α↓	炎症反应↓，免疫微环境、唾液分泌↑	[34]
	miR-23b-3p（↑）	NOD小鼠	NF-κB	TNF-α、IL-6、IL-17A、ING-γ↓，TGF-β1↑，Th1/Th17/Treg平衡	炎症反应↓，唾液分泌↑	[36]
	miR-146a-5p（↑）	SS患者	IL23/IL23R	ADAM17↓，IL-17A、IL-21↑，Th17细胞↑，Th17分化↑	免疫炎症反应↓	[40]
调节T/B 淋巴细胞	miR-216a-3p（-）	pSS大鼠	JAK/STAT	AFF-R、BCR、TLR-9↓，B细胞活化↓； TNF-α、IFN-γ、IL-6↓	炎症反应、组织纤维化↓、唾液分泌↑	[42]
	miR-10a-5p（-）	ESS小鼠	-	Bcl-6↓，B细胞数量、活化↓	唾液腺功能↑	[44]
	miR-125b（-）	SS患者、NOD小鼠	-	PRDM1↓，B细胞活化↓；CD19CD20CD27CD38细胞比例↓	炎症反应、腺体损伤↓，唾液流速、唾液分泌↑	[46]
	hsa-miR-30b-5p （↑）	SS患者	-	B细胞活化↓	炎症浸润↓，腺体功能↑	[48]
	hsa-miR-3202（-）	SS患者	-	MMP2↓，T细胞浸润、增殖侵袭↓	免疫炎症反应、唇腺损伤↓，腺体功能、唾液分泌↑	[49]
	miR-142-3p（↓）	SS患者	-	cAMP生成↓，钙信号↓，蛋白质生成↓；T细胞激活↑	上皮细胞功能、腺体功能↑	[53]
	miR-let-7d-3p（↑）	SS患者	AKT1/mTOR	CD4⁺T比例↓，IL-17↓	炎症反应↓	[57]
	miR-31-5p（↓）	SS患者	-	ECAR、OCR↓，葡萄糖代谢↑， T细胞反应↑	炎症反应↓	[59]
调节腺体功能	ebv-miR-BART13-3p（↓）	SS患者	-	STIM1↑、SOCE↑、钙依赖性基因↑、AQP5↑	腺体功能、唾液分泌↑	[62]
调节Ⅰ型 IFN反应	hsa-miR-145-5p（↑）	SS患者、HSG细胞	-	MUC1、TLR4、I型IFN↓	炎症反应↓，腺体功能↑	[64]
调节Ⅰ型 IFN反应	miR-744-5p（↓）	SS患者	-	PELI3↑，CCL5、CXCL10↓	炎症反应↓	[66]
调节其他机制	hsa-miR-181d-5p（↑）	SS患者	-	TNF-α介导炎症反应↓	腺体损伤↓，唾液分泌↑	[68]
调节其他机制	miR-130a、miR-708（↑）	SS患者	-	MSK1↓，cDC2激活↓，TNF-α、IL-6、 IL-12↓	炎症反应↓	[72]

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