Curculigoside Attenuates Endoplasmic Reticulum Stress-Induced Epithelial Cell and Fibroblast Senescence by Regulating the SIRT1-P300 Signaling Pathway DOI Creative Commons

Weixi Xie,

Lang Deng, Rui Qian

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 420 - 420

Published: March 29, 2024

The senescence of alveolar epithelial cells (AECs) and fibroblasts plays a pivotal role in the pathogenesis idiopathic pulmonary fibrosis (IPF), condition lacking specific therapeutic interventions. Curculigoside (CCG), prominent bioactive constituent Curculigo, exhibits anti-osteoporotic antioxidant activities. Our investigation aimed to elucidate anti-senescence anti-fibrotic effects CCG experimental delineate its underlying molecular mechanisms. findings demonstrate that attenuates bleomycin-induced lung murine models, concomitantly ameliorating function impairment. Immunofluorescence staining for marker p21, alongside SPC or α-SMA, suggested CCG’s mitigation correlates closely with deceleration AECs fibroblasts. In vitro, mitigated H2O2-induced natural primary mouse Mechanistically, can upregulate SIRT1 expression, downregulating P300 enhancing Trim72 expression facilitate ubiquitination degradation, reducing acetylation levels enzymes, upregulating their levels. These actions collectively inhibited endoplasmic reticulum stress (ERS) alleviated senescence. Furthermore, mechanisms were validated D-galactose (D-gal)-induced progeroid model. This study provides novel insights into action cellular chronic diseases, offering potential avenues development innovative drugs strategies.

Language: Английский

mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice DOI Creative Commons

Nan‐Shi‐Yu Yang,

Wenjing Zhong,

Han-Xi Sha

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(5), P. 1927 - 1946

Published: Jan. 1, 2024

The activation of NLRP3 inflammasome in microglia is critical for neuroinflammation during postoperative cognitive dysfunction (POCD) induced by sevoflurane.However, the molecular mechanism which sevoflurane activates remains unclear.The cGAS-STING pathway an evolutionarily conserved inflammatory defense mechanism.The role sevoflurane-induced inflammasome-dependent and underlying mechanisms require further investigation.We found that prolonged anesthesia with triggered characterized vivo.Interestingly, was activated hippocampus mice receiving sevoflurane.While blockade cGAS RU.521 attenuated mice.In vitro, we treatment significantly microglia, while pre-treatment robustly inhibited activation.Mechanistically, mitochondrial fission released DNA (mtDNA) into cytoplasm, could be abolished Mdivi-1.Blocking mtDNA release via mPTP-VDAC channel inhibitor cytosolic escape reduced finally inhibiting activation.Therefore, regulating targeting may provide a novel therapeutic target POCD.

Language: Английский

Citations

19
ALKBH5 SUMOylation-mediated FBXW7 m6A modification regulates alveolar cells senescence during 1-nitropyrene-induced pulmonary fibrosis DOI

Se-Ruo Li,

Ningning Kang,

Rongrong Wang

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 468, P. 133704 - 133704

Published: Feb. 9, 2024

Language: Английский

Citations

13
The role of epithelial cells in fibrosis: Mechanisms and treatment DOI Creative Commons

Liuyi Luo,

Wei Zhang,

Siyao You

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107144 - 107144

Published: March 13, 2024

Fibrosis is a pathological process that affects multiple organs and considered one of the major causes morbidity mortality in diseases, resulting an enormous disease burden. Current studies have focused on fibroblasts myofibroblasts, which directly lead to imbalance generation degradation extracellular matrix (ECM). In recent years, increasing number role epithelial cells fibrosis. some cases, are first exposed external physicochemical stimuli may drive collagen accumulation mesenchyme. other source stimulation mainly immune cytokines, similarly altered process. this review, we will focus dynamic alterations involved after injury during fibrogenesis, discuss association among them, summarize therapies targeting changed cells. Especially, mesenchymal transition (EMT) key central step, closely linked biological behaviors. Meanwhile, think disruption barrier, cell death basal stem populations stemness fibrosis not appreciated. We believe targeted can prevent progress fibrosis, but reverse it. The provide wonderful preventive delaying action.

Language: Английский

Citations

10
Morusin Alleviates Aortic Valve Calcification by Inhibiting Valve Interstitial Cell Senescence Through Ccnd1/Trim25/Nrf2 Axis DOI Creative Commons
Zongtao Liu, Kan Wang, Chen Jiang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(20)

Published: March 19, 2024

Abstract The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression calcific disease (CAVD). However, precise mechanisms underlying VICs remain unclear, demanding identification novel target to mitigate this process. Previous studies have highlighted anti‐aging potential morusin. Thus, study aimed explore therapeutic morusin CAVD. Cellular experiments reveal that effectively suppresses cellular and cause shift toward osteogenic differentiation vitro. Mechanistically, activate Nrf2‐mediated antiaging signaling pathway by downregulating CCND1 expression aiding Keap1 degradation through Trim 25. This activation lead upregulated antioxidant genes, thus reducing reactive oxygen species production thereby preventing VIC differentiation. In vivo ApoE −/− mice on high‐fat Western diet demonstrate positive effect mitigating calcification. These findings emphasize properties its as agent for

Language: Английский

Citations

10
Melatonin protects against cadmium-induced endoplasmic reticulum stress and ferroptosis through activating Nrf2/HO-1 signaling pathway in mice lung DOI

Ziyang Huang,

Rui‐Jia Xu,

Zhongjun Wan

et al.

Food and Chemical Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 115324 - 115324

Published: Feb. 1, 2025

Language: Английский

Citations

1
Tetrandrine alleviates pulmonary fibrosis by inhibiting alveolar epithelial cell senescence through PINK1/Parkin-mediated mitophagy DOI

Lanhe Chu,

Jinzhong Zhuo,

Haohua Huang

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 969, P. 176459 - 176459

Published: March 2, 2024

Language: Английский

Citations

8
Melatonin Mitigates Atrazine-Induced Renal Tubular Epithelial Cell Senescence by Promoting Parkin-Mediated Mitophagy DOI Creative Commons
Yu-Sheng Shi,

Tian‐Ning Yang,

Yuxiang Wang

et al.

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

The accumulation of senescent cells in kidneys is considered to contribute age-related diseases and organismal aging. Mitochondria are a regulator cell senescence process. Atrazine as triazine herbicide poses threat renal health by disrupting mitochondrial homeostasis. Melatonin plays critical role maintaining present study aims explore the mechanism which melatonin alleviates atrazine-induced injury whether parkin-mediated mitophagy contributes mitigating senescence. found that level parkin was decreased after atrazine exposure negatively correlated with markers. treatment increased serum levels mitigates tubular epithelial Mechanistically, maintains integrity crista structure increasing contact site cristae organizing system, transcription factor A (TFAM), adenosine triphosphatase family AAA domain-containing protein 3A (ATAD3A), sorting assembly machinery 50 (Sam50) prevent DNA release subsequent activation cyclic guanosine 5′-monophosphate–adenosine 5′-monophosphate synthase pathway. Furthermore, activates Sirtuin 3–superoxide dismutase 2 axis eliminate reactive oxygen species kidney. More importantly, antisenescence largely determined parkin-dependent mitophagy. These results offer novel insights into measures against Parkin-mediated promising drug target for alleviating

Language: Английский

Citations

7
Wnt5a-mediated autophagy contributes to the epithelial-mesenchymal transition of human bronchial epithelial cells during asthma DOI Creative Commons

Yu‐Biao Liu,

Xiaohua Tan, Hui‐Hui Yang

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: June 19, 2024

Abstract Background The epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBECs) is essential for airway remodeling during asthma. Wnt5a has been implicated in various lung diseases, while its role the EMT HBECs asthma yet to be determined. This study sought define whether initiated EMT, leading through induction autophagy HBECs. Methods Microarray analysis was used investigate expression change WNT5A patients. In parallel, models were induced using 16HBE by exposing them house dust mites (HDM) or interleukin-4 (IL-4), and then observed. Using vitro gain- loss-of-function approaches via mimic peptide FOXY5 inhibitor BOX5, alterations marker E-cadherin mesenchymal protein Mechanistically, Ca 2+ /CaMKII signaling pathway evaluated. An 3-MA examine regulation EMT. Furthermore, we a CaMKII KN-93 determine overactivation pathway. Results Asthma patients exhibited significant increase gene compared healthy control. Upon HDM IL-4 treatments, observed that levels significantly increased cells. Interestingly, inhibited upregulated α-SMA, Collagen I, proteins (Beclin1 LC3-II). Rhodamine-phalloidin staining showed resulted rearrangement cytoskeleton an quantity stress fibers Importantly, blocking with BOX5 reduced caused FOXY5, as well fibers, cell adhesion, autophagy. Conclusion illustrates new link Wnt5a-Ca /CaMKII-autophagy axis triggering remodeling. Our findings may provide novel strategies treatment EMT-related diseases.

Language: Английский

Citations

5
Cardioprotective Response and Senescence in Aged sEH Null Female Mice Exposed to LPS DOI
Ala Yousef, Deanna K. Sosnowski, Liye Fang

et al.

AJP Heart and Circulatory Physiology, Journal Year: 2024, Volume and Issue: 326(6), P. H1366 - H1385

Published: April 5, 2024

Soluble epoxide hydrolase (sEH) is an essential enzyme for converting epoxy fatty acids to their less bioactive diols. Our study suggests deletion or inhibition of sEH impacts the aging process in hearts female mice resulting cardioprotection. Data indicate targeting limits inflammation, preserves mitochondria, and alters cellular senescence aged heart.

Language: Английский

Citations

4
TRIM25: A Global Player of Cell Death Pathways and Promising Target of Tumor-Sensitizing Therapies DOI Creative Commons
W. Eberhardt, Usman Nasrullah,

Josef Pfeilschifter

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 65 - 65

Published: Jan. 7, 2025

Therapy resistance still constitutes a common hurdle in the treatment of many human cancers and is major reason for failure patient relapse, concomitantly with dismal prognosis. In addition to “intrinsic resistance”, e.g., acquired by random mutations, cancer cells typically escape from certain treatments (“acquired resistance”) large variety means, including suppression apoptosis other cell death pathways via upregulation anti-apoptotic factors or through inhibition tumor-suppressive proteins. Therefore, ideally, tumor-cell-restricted induction considered promising avenue development novel, tumor (re)sensitizing therapies. A growing body evidence has highlighted multifaceted role tripartite motif 25 (TRIM25) controlling different aspects tumorigenesis, chemotherapeutic drug resistance. Accordingly, overexpression TRIM25 observed tumors frequently correlates poor survival. its originally described function antiviral innate immune response, can play critical yet context-dependent roles apoptotic- non-apoptotic-regulated pathways, pyroposis, necroptosis, ferroptosis, autophagy. The review summarizes current knowledge molecular mechanisms which interfere modalities thereby affect success currently used chemotherapeutics. better understanding complex repertoire modulatory effects an essential prerequisite validating as potential target future anticancer therapy surmount high rate chemotherapies.

Language: Английский

Citations

0