Immunity Inflammation and Disease
·
2023
·Vol. 11
·期 5
·e814
·
IF 3.2
Hecheng Wang,Jiadan Teng,Mingtao Wang,Yuhang Zhang,Xiaoshuang Liu,Zhuya Liu
Background Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been reported to play regulatory roles in ulcerative colitis (UC). In this study, we aimed to determine the specific roles and action mechanism of the nuclear paraspeckle assembly transcript 1 ( NEAT1 ) in UC. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the lncRNA NEAT1 and miR-493-5p expression levels in patients with UC and healthy volunteers. We determine the forecast linkage points of NEAT1 and miR-493-5p using Starbase and those of miR-493-5p and Rab27A using TargetScan, and further verified them using a double luciferase gene reporter kit. RT-qPCR and Western blot analysis were used to determine the lncRNA NEAT1 , miR-493-5p , and Rab27A expression levels in lipopolysaccharide (LPS)-induced Caco-2 cells. Flow cytometry and cell counting kit-8 were used to assess Caco-2 cell viability. Tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-1β levels were determined via an enzyme-linked immunosorbent assay. Results Expression levels of NEAT1 were upregulated and those of miR-493-5p were downregualted in 10 ng/mL LPS-treated Caco-2 cells and patients with UC. Dual-luciferase gene reporter assay revealed that miR-493-5p is linked to NEAT1 , and Rab27A is a downstream target of miR-493-5p . Overexpression of miR-493- 5p inhibited the apoptosis and inflammation in LPS-treated Caco-2 cells. Moreover, downregulation of lncRNA NEAT1 expression also inhibited the apoptosis and inflammation in LPS-treated Caco-2 cells, which was reversed by Rab27A plasmid cotransfection. Conclusion Our results revealed that NEAT1 participates in UC progression by inhibiting miR-493-5p expression.
研究领域:
分子生物学
·
胃肠病学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Extracellular Vesicles
·
2025
·Vol. 14
·期 9
·e70162
·
IF 14.5
Bin Liu,Yansi Xian,Tao Shen,Yu Ben,Wenshu Wu,Yong Shi,Xueying An,Rui Peng,Wentian Gao,Wang Gong,Xiang Chen,Baosheng Guo,Qing Jiang
Osteoarthritis (OA), the prevalent debilitating joint disorder, is accelerated by dysregulated intercellular crosstalk, yet the role of fibroblast-like synoviocyte (FLS)-derived extracellular vesicles and particles (EVPs) in disease progression remains to be elucidated. Here, integrative analysis of clinical specimens, animal models, and publicly available datasets revealed significant alterations in exosomal pathways within OA synovium. Proteomic profiling revealed distinct molecular signatures in EVPs derived from inflammatory and senescent FLSs, reflecting the pathophysiological status of their parent cells. We demonstrated that FLSs under inflammatory and senescent states in OA secreted pathogenic EVPs that propagated joint degeneration by disrupting chondrocyte homeostasis, polarizing macrophages towards a pro-inflammatory phenotype, and impairing chondrogenesis of mesenchymal stem cells. To therapeutically target these pathogenic EVPs, we engineered an adeno-associated virus 9 (AAV9) vector fused with a synovium-affinity peptide (HAP-1) to deliver shRNA against Rab27a , a key regulator of EVP secretion. Intra-articular administration of the engineered AAV9 in a murine OA model induced by destabilization of the medical meniscus significantly reduced synovial hyperplasia, cartilage degradation and inflammatory responses, while demonstrating satisfactory systemic biosafety. Our findings establish FLS-derived EVPs as critical mediators of OA pathogenesis and propose a targeted strategy to block their secretion, offering a promising disease-modifying therapeutic avenue for OA. Graphical Osteoarthritis (OA) progression involves pathogenic extracellular vesicles and particles (EVPs) from inflamed/senescent fibroblast-like synoviocytes (FLSs). Proteomic profiling revealed that pathogenic EVPs contribute to OA progression by disrupting the homeostasis of macrophages, chondrocytes and mesenchymal stem cells. Targeted inhibition of FLS-derived exosomes effectively alleviated OA progression with good biosafety.
研究领域:
分子生物学
·
生物化学
·
细胞生物学
·
蛋白质组学
·
基因治疗
·
病毒学
·
免疫学
·
风湿病学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Lv Jinpeng,An Xiaohong,Jiang Songzhou,Yang Ying,Song Guoqiang,Gao Rongyin
Protoporphyrin IX (PPIX) is a heterocyclic organic compound that is the last intermediate in the heme biosynthetic pathway. PPIX, due to its photodynamic effects, is utilized in the treatment of skin diseases. Furthermore, PPIX has been utilized as a melanogenesis-stimulating agent in various studies. However, the exact function and mechanism underlying PPIX action in melanocytes remain to be elucidated. In the present study, we sought to further investigate how PPIX affects melanocyte melanogenesis, and whether PPIX is involved in melanin transport. Our findings demonstrated that PPIX increased melanocyte dendricity and melanosome transport, in addition to increasing melanogenesis. PPIX functions primarily by activating the guanylate cyclase (GC) and cyclic guanosine 3’, 5’-monophosphate/protein kinase G (cGMP/PKG) signaling pathways. Once activated, these pathways increase tyrosinase activity and the expression of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2), myosin Va, melanophinin, Ras-related protein Rab-27A (Rab27a), and cell division cycle 42 (Cdc42), promoting melanogenesis, melanocyte dendricity, and melanosome transport. Furthermore, the melanogenic effects of PPIX were confirmed in vivo in a zebrafish model system. Our results indicate that PPIX is not cytotoxic and may, thus, be utilized as a pigmentation enhancer.
研究领域:
细胞生物学
·
分子生物学
·
药理学
·
皮肤病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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