TL1A/TNFR2‐mediated mitochondrial dysfunction of fibroblast‐like synoviocytes increases inflammatory response in patients with rheumatoid arthritis via reactive oxygen species generation

Al‐Azab, Mahmoud; Qaed, Eskandar; Ouyang, Xunli; Elkhider, Abdalkhalig; Walana, Williams; Han, Li; Li, Weiping; Tang, Yawei; Adlat, Salah; Wei, Jing; Wang, Bing; Li, Xia

doi:10.1111/febs.15181

Cited by 28 publications

(12 citation statements)

References 44 publications

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“…Proteins were extracted from more than 10 6 harvested BMSCs according to the kit protocol (KeyGen Biotech, China). [46] BMSCs were digested in a lysis buffer cocktail and centrifuged at 12000 g for 15 minutes at 4…”

Section: Western Blotmentioning

confidence: 99%

Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway

Al‐Azab

Wang

Elkhider

et al. 2020

Aging

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Premature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.

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Section: Western Blotmentioning

confidence: 99%

Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway

Al‐Azab

Wang

Elkhider

et al. 2020

Aging

Self Cite

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“…Intracellular ROS generation was quantified with a Fluorometric Intracellular ROS Kit (MAK144, Sigma-Aldrich), which was used to assess mitochondrial damage and to measure intracellular ROS production (Al-Azab et al, 2020). The H9c2 cells were treated with H/R or TBHP, the culture media were disposed, and then, 100 uL/well of master reaction mix were added into the cell plate and incubated at 37°C for 30 min.…”

Section: Ros Detectionmentioning

confidence: 99%

Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway

et al. 2021

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Although miR-327 had a protective effect on cardiomyocytes as described previously, the potential mechanism still needs further exploration. The aim of this study was to investigate the role and mechanism of miR-327 on oxidative stress in myocardial ischemia/reperfusion injury (MI/RI) process. Oxidative stress and cardiomyocytes injury were detected in rat model of MI/RI, hypoxia/reoxygenation (H/R), and tert-butyl hydroperoxide (TBHP) model of H9c2 cells. In vitro, downregulation of miR-327 inhibited both H/R- and TBHP-induced oxidative stress, and suppressed apoptosis. Meanwhile, fibroblast growth factor 10(FGF10) was enhanced by miR-327 knocked down, followed by the activation of p-PI3K and p-Akt, and the translocation of Nrf2. However, miR-327 overexpression performed with opposite effects. Consistent with the results in vitro, downregulation of miR-327 attenuated reactive oxygen species (ROS) generation as well as intrinsic apoptosis, and alleviated I/R injury. In conclusion, inhibition of miR-327 improved antioxidative ability and myocardial cell survival via regulating the FGF10/Akt/Nrf2 pathway.

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“…Tumor necrosis factor (TNF)-like cytokine 1A (TL1A), which belongs to the TNF superfamily, plays critical roles in the development of chronic inflammation [ 82 ]. TL1A receptors include decoy receptor 3 (DcR3), and death receptor 3 belongs to the TNF receptor superfamily [ 83 ].…”

Section: Targetsmentioning

confidence: 99%

Decoy Technology as a Promising Therapeutic Tool for Atherosclerosis

Mahjoubin‐Tehran

Teng

Jalili

et al. 2021

IJMS

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Cardiovascular diseases (CVDs) have been classified into several types of disease, of which atherosclerosis is the most prevalent. Atherosclerosis is characterized as an inflammatory chronic disease which is caused by the formation of lesions in the arterial wall. Subsequently, lesion progression and disruption ultimately lead to heart disease and stroke. The development of atherosclerosis is the underlying cause of approximately 50% of all deaths in westernized societies. Countless studies have aimed to improve therapeutic approaches for atherosclerosis treatment; however, it remains high on the global list of challenges toward healthy and long lives. Some patients with familial hypercholesterolemia could not get intended LDL-C goals even with high doses of traditional therapies such as statins, with many of them being unable to tolerate statins because of the harsh side effects. Furthermore, even in patients achieving target LDL-C levels, the residual risk of traditional therapies is still significant thus highlighting the necessity of ongoing research for more effective therapeutic approaches with minimal side effects. Decoy-based drug candidates represent an opportunity to inhibit regulatory pathways that promote atherosclerosis. In this review, the potential roles of decoys in the treatment of atherosclerosis were described based on the in vitro and in vivo findings.

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TL1A/TNFR2‐mediated mitochondrial dysfunction of fibroblast‐like synoviocytes increases inflammatory response in patients with rheumatoid arthritis via reactive oxygen species generation

Cited by 28 publications

References 44 publications

Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway

Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway

Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway

Decoy Technology as a Promising Therapeutic Tool for Atherosclerosis

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