Curcumin nicotinate suppresses abdominal aortic aneurysm pyroptosis via lncRNA PVT1/miR-26a/KLF4 axis through regulating the PI3K/AKT signaling pathway

Xiong, Jian-Ming; Liu, Hui; Chen, Jie; Zou, Qianli; Wang, Yang-Yi-Jing; Bi, Guoshan

doi:10.1093/toxres/tfab041

Cited by 19 publications

(13 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This process is accompanied by the release of many inflammatory factors such as IL‐1β and IL‐18, which ultimately magnifies the local inflammatory response. Xiong et al found that regulation of vascular smooth muscle cell pyroptosis could constrain AAA [ 46 ]. Moreover, macrophage pyroptosis has been suggested to be involved in AAA [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome

Jiang

et al. 2022

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Preclinical studies have suggested that adipose-derived mesenchymal stem cells (ADSCs) transplantation can suppress abdominal aortic inflammation and aneurysm expansion through paracrine factors. Yet, the mechanism of action is not fully understood. In the present study, we further examined the function and mechanism of ADSC-derived exosomes (ADSC-exos) and their microRNA-17-5p (miR-17-5p) on the abdominal aortic aneurysm (AAA) progression. Methods ADSC-exos were isolated and identified. DiR and PKH67 staining were used to trace ADSC-exo in vivo and in vitro. Raw264.7 cells were applied to perform in vitro experiments, while a murine AAA model induced using angiotensin II (Ang II) was used for in vivo testing. The expression level of miR-17-5p in macrophages and Ang II-treated macrophages after ADSC-exos treatment was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The target relation between miR-17-5p and thioredoxin-interacting protein (TXNIP) was identified by a dual-luciferase reporter gene assay. Artificial activation and block of experiments of miR-17-5p and TXNIP were conducted to clarify their functions in inflammation during AAA progression. The severity of AAA between groups was assessed by maximal aorta diameter, AAA incidence, survival rate, and histological stainings. Besides, inflammasome-related proteins and macrophage pyroptosis were further evaluated using western blot, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA). Results The ADSC-exos were isolated and identified. In vivo testing showed that ADSC-exos were mainly distributed in the liver. Meanwhile, in vitro experiments suggested that ADSC-derived exosomes were taken up by macrophages, while inside, ADSC-exos miR-17-5p decreased a TXNIP induced by Ang II by directly binding to its 3′-untranslated region (3’UTR). Furthermore, overexpression of miR-17-5p enhanced the therapeutic function of ADSC-exos on inflammation during AAA expansion in vivo, while its inhibition reversed this process. Finally, overexpressed TXNIP triggered macrophage pyroptosis and was alleviated by ADSC-derived exosomes in vitro. Conclusion ADSC-exos miR-17-5p regulated AAA progression and inflammation via the TXNIP-NLRP3 signaling pathway, thus providing a novel insight in AAA treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome

Jiang

et al. 2022

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…In line with our data, KLF4 upregulation increased the levels of oxidative stress markers and proinflammatory cytokines in LPS-treated ATDC5 cells in ankylosing spondylitis (52), and KLF4 deficiency imparts an anti-inflammation role in dextran sodium sulfate–triggered colitis (53). Moreover, decreased KLF4 expression diminishes pyroptosis of Ang-II–treated vascular smooth muscle cells by blocking the PI3K/AKT signaling pathway (54). Collectively, the above evidence indicated that KLF4 upregulation neutralized the suppression of silencing USP25 on pyroptosis in AP induced by LPS and CRE.…”

Section: Discussionmentioning

confidence: 99%

Usp25 Upregulation Boosts GSDMD-Mediated Pyroptosis of Acinar Cells in Acute Pancreatitis

Liu

Zhang

2022

Shock

View full text Add to dashboard Cite

Acute pancreatitis (AP) is an inflammation-associated disorder in the digestive system. Ubiquitin-specific peptidase 25 (USP25) can modulate inflammation in diseases. This study expounded on the role of USP25 in pyroptosis of acinar cells in AP. Acinar cells were treated with lipopolysaccharide (LPS) and caerulein (CRE) to induce AP. Afterward, the expression patterns of USP25, microRNA (miR)-10a-5p, and Krüppel-like factor 4 (KLF4) in acinar cells were examined. Then, acinar cell viability and levels of NLR family pyrin-domain containing 3 (NLRP3), cleaved caspase-1, cleaved N-terminal gasdermin D (GSDMD-N), interleukin (IL)-1β, and IL-18 were determined. We observed that USP25 was highly expressed in AP models, and silencing USP25 increased cell viability and inhibited pyroptosis of AP acinar cells. The bindings of USP25 to KLF4 and miR-10a-5p to KLF4 and the GSDMD 3′UTR sequence were validated. We found that USP25 binding to KLF4 inhibited ubiquitination degradation of KLF4, KLF4 transcriptionally decreased miR-10a-5p expression, and miR-10a-5p targeted GSDMD expression. Finally, rescue experiments proved that KLF4 overexpression or miR-10a-5p suppression enhanced pyroptosis of AP acinar cells. Overall, USP25 stabilized KLF4 expression through deubiquitination, limited miR-10a-5p expression, and increased GSDMD expression, finally promoting pyroptosis of acinar cells in AP.

show abstract

“…Therefore, we explored the molecular mechanism underlying PVT1-mediated AAA progression in the H 2 O 2 induced VSMCs injury model. In an in vitro model of AAA, PVT1 knockout not only inhibited VSMC apoptosis and ECM disruption, but also suppressed VSMC pyroptosis and inflammation [ 22 , 23 ]. We also found that the high expression of PVT1 in AAA tissues and PVT1 silencing increased VSMC proliferation, blunted the apoptosis rate, and alleviated inflammatory events in the H 2 O 2 -induced apoptotic model of VSMCs.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, Xiong et al . also reported that the promotion of AAA by PVT1 is mediated by the miR-26a/KLF4 axis through the PI3K/AKT signaling pathway [ 23 ]. In contrast, NCKAP1L loss blunts AKT phosphorylation and modulates immunodeficiency [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…recently found that the lncRNA PVT1 promoter blunted oncogenic MYC transcription, and suppressed breast cancer tumorigenesis in vivo [ 21 ]. Interestingly, the inhibitory effect of lncRNA PVT1 on VSMC apoptosis and ECM disruption was also detected in a murine AAA model [ 22 , 23 ]. However, the underlying mechanisms remain to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Long non-coding RNA PVT1/microRNA miR-3127-5p/NCK-associated protein 1-like axis participates in the pathogenesis of abdominal aortic aneurysm by regulating vascular smooth muscle cells

Huang

et al. 2021

Bioengineered

View full text Add to dashboard Cite

The long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) has been implicated in the progression of abdominal aortic aneurysms (AAA). However, the detailed mechanism requires further analysis. Our study was aimed at interrogating the mechanism of PVT1 in an H 2 O 2 -induced AAA model in vitro . The expression of lncRNA PVT1, microRNA miR-3127-5p, and NCK-associated protein 1-like (NCKAP1L) was examined in AAA tissues and H 2 O 2 -treated vascular smooth muscle cells (VSMCs). Cell proliferation was assayed using Cell Counting Kit-8 (CCK8) and 5-Bromodeoxyuridine (BrdU) assays. Meanwhile, 5-Ethynyl-2′-deoxyuridine (EdU) staining was performed to assess cell apoptosis and caspase-3 activity. IL-1β and caspase-1 expression was also assessed using Western blotting to determine inflammasome activation in H 2 O 2 -treated VSMCs. Luciferase reporter assays addressed the possible interaction between miR-3127-5p and PVT1 or NCKAP1L, which was predicted by starBase analysis. PVT1 and NCKAP1L expression was elevated in AAA tissues and induced the AAA model in vitro , whereas miR-3127-5p showed the opposite trend. Functionally, PVT1 silencing promoted cell proliferation and reduced the apoptotic rate and inflammasome activation in H 2 O 2 -treated VSMCs. Mechanical investigation demonstrated that PVT1 acted as a sponge of miR-3127-5p to modulate NCKAP1L expression, resulting in suppression of VSMC proliferation, induction of apoptosis, and activation of inflammation. In conclusion, PVT1 participates in AAA progression through the miR-3127-5p/NCKAP1L axis and may be a promising biosignature and therapeutic target for AAA.

show abstract

Curcumin nicotinate suppresses abdominal aortic aneurysm pyroptosis via lncRNA PVT1/miR-26a/KLF4 axis through regulating the PI3K/AKT signaling pathway

Cited by 19 publications

References 36 publications

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome

Usp25 Upregulation Boosts GSDMD-Mediated Pyroptosis of Acinar Cells in Acute Pancreatitis

Long non-coding RNA PVT1/microRNA miR-3127-5p/NCK-associated protein 1-like axis participates in the pathogenesis of abdominal aortic aneurysm by regulating vascular smooth muscle cells

Contact Info

Product

Resources

About