GDF15/MIC-1: a stress-induced immunosuppressive factor which promotes the aging process DOI Creative Commons
Antero Salminen

Biogerontology, Journal Year: 2024, Volume and Issue: 26(1)

Published: Dec. 6, 2024

Abstract The GDF15 protein, a member of the TGF-β superfamily, is stress-induced multifunctional protein with many its functions associated regulation immune system. signaling provides defence against excessive inflammation induced by diverse stresses and tissue injuries. Given that aging process low-grade inflammatory state, called inflammaging, it not surprising expression gradually increases aging. In fact, core factor secreted senescent cells, state senescence-associated secretory phenotype (SASP). Many age-related stresses, e.g., mitochondrial endoplasmic reticulum as well inflammatory, metabolic, oxidative induce GDF15. Although an effective anti-inflammatory modulator, there robust evidence pro-aging promoting process. only modulator but also potent immunosuppressive enhancer in chronic states. can stimulate responses either non-specifically via receptors superfamily or specifically through GFRAL/HPA/glucocorticoid pathway. stimulates network activating MDSCs, Tregs, M2 macrophages triggering inhibitory checkpoint cells. Immunosuppressive suppress processes they evoke detrimental effects aged tissues, such cellular senescence, fibrosis, atrophy/sarcopenia. It seems survival go awry persistent thus diseases.

Language: Английский

GDF15-mediated enhancement of the Warburg effect sustains multiple myeloma growth via TGFβ signaling pathway DOI Creative Commons

Wenjing Xue,

Ying Li, Ye Ma

et al.

Cancer & Metabolism, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 27, 2025

The Warburg effect, characterized by the shift toward aerobic glycolysis, is closely associated with onset and advancement of tumors, including multiple myeloma (MM). Nevertheless, specific regulatory mechanisms glycolysis in MM its functional role remain unclear. In this study, we identified that growth differentiation factor 15 (GDF15) a glycolytic regulator, GDF15 highly expressed cells patient samples. Through gain-of-function loss-of-function experiments, demonstrated promotes cell proliferation inhibits apoptosis. Moreover, enhances Warburg-like metabolism cells, as evidenced increased glucose uptake, lactate production, extracellular acidification rate, while reducing oxidative phosphorylation. Importantly, tumor-promoting effects are fermentation-dependent. Mechanistically, was found to promote expression key genes, particularly transporter GLUT1, through activation TGFβ signaling pathway. Pharmacological inhibition pathway effectively abrogated oncogenic activities proliferation, apoptosis, fermentation. vivo experiments using subcutaneous xenotransplanted tumor model confirmed knockdown led significant reduction growth, overexpression promoted growth. Overall, our study provides insights into molecular underlying pathogenesis highlights potential targeting GDF15-TGFβ -glycolysis axis therapeutic approach for future interventions MM.

Language: Английский

Citations

0
USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer DOI Creative Commons

Zhongdong Xie,

Hanbin Lin,

Yuecheng Wu

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 8, 2025

Language: Английский

Citations

0
Growth Differentiation Factor 15 Inhibits Cardiac Fibrosis, Oxidative Stress, Inflammation, and Apoptosis in a Rat Model of Heart Failure with Preserved Ejection Fraction DOI Creative Commons
Xuyang Meng, Yi Li, Ling‐bing Meng

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 18, 2025

Background: Heart failure with preserved ejection fraction (HFpEF) is a systemic syndrome primarily associated fibrosis, oxidative stress, inflammation, and cellular apoptosis. Growth differentiation factor 15 (GDF15), biomarker commonly used in clinical studies, exhibits protective effects on the myocardium. Therefore, focus of present study to determine mechanism by which GDF15 protects cardiac function HFpEF. Methods: We conducted functional enrichment analysis protein-protein interaction network genes highly expressed HFpEF but lowly normal samples. established an rat model feeding rats high-fat diet administering N-omega-nitro-l-arginine-methyl ester (L-NAME) their drinking water silenced tail vein injection lentivirus (L3110). After 12 weeks feeding, echocardiographic examinations were performed. Following euthanasia rats, blood heart tissue samples collected. sections stained using Masson’s trichrome terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining methods. Western blot (WB) was employed concentrations relevant proteins. Results: The results showed that compared + MOCK group, HFpEF+silencing (siGDF15) group exhibited more severe dysfunction, significant decreases (p < 0.05) E/A ratio 0.001). WB demonstrated that, HFpEF+siGDF15 increased expression fibrosis-associated proteins, including collagen I 0.01), III α-smooth muscle actin (α-SMA) 0.01). Additionally, stress-associated biomarkers such as myeloperoxidase (MPO) 0.01) oxidized low-density lipoprotein (ox-LDL) inflammation-associated biomarkers, interleukin-1 beta (IL-1β) interleukin-6 (IL-6) interleukin-8 (IL-8) tumor necrosis α (TNFα) apoptosis-associated like cleaved caspase-3 BCL2-associated X (BAX) also upregulated group. Conclusions: Our research indicates preserves inhibiting myocardial reducing cell alleviating suppressing

Language: Английский

Citations

0
3D printed GelMA/HAMA based mechanical microenvironment boosted PDAC chemoresistance via NRF2-repressed ferroptosis DOI

Jiashuai Yan,

Di Wu,

Biwen Zhu

et al.

Colloids and Surfaces B Biointerfaces, Journal Year: 2025, Volume and Issue: 254, P. 114816 - 114816

Published: May 26, 2025

Language: Английский

Citations

0
The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials DOI Creative Commons

Yi Pei,

Jianqiao Yin,

Jiamei Liu

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101358 - 101358

Published: June 1, 2025

Language: Английский

Citations

0
Duocarmycin SA Reduces Proliferation and Increases Apoptosis in Acute Myeloid Leukemia Cells In Vitro DOI Open Access
William A. Chen,

Terry G Williams,

Leena So

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4342 - 4342

Published: April 14, 2024

Acute myeloid leukemia (AML) is a hematological malignancy that characterized by an expansion of immature precursors. Despite therapeutic advances, the prognosis AML patients remains poor and there need for evaluation promising candidates to treat disease. The objective this study was evaluate efficacy duocarmycin Stable A (DSA) in cells vitro. We hypothesized DSA would induce DNA damage form double-strand breaks (DSBs) exert cytotoxic effects on within picomolar range. Human cell lines Molm-14 HL-60 were used perform 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), DSBs, cycle, 5-ethynyl-2-deoxyuridine (EdU), colony formation unit (CFU), Annexin V, RNA sequencing other assays described study. Our results showed induced cycle arrest at G2M phase, reduced proliferation increased apoptosis cells. Additionally, regulates genes are associated with cellular processes such as repair, checkpoint apoptosis. These suggest efficacious therefore potential candidate can be further evaluated treatment AML.

Language: Английский

Citations

2
MGST3 regulates BACE1 protein translation and amyloidogenesis by controlling the RGS4-mediated AKT signaling pathway DOI Creative Commons

Yalan Pu,

Jie Yang,

Qiuling Pan

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(8), P. 107530 - 107530

Published: July 4, 2024

Language: Английский

Citations

2
The role of GDF15 in attenuating noise-induced hidden hearing loss by alleviating oxidative stress DOI Creative Commons
Yihong Jiang, Zeyu Zheng,

Jing Zhu

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Sept. 18, 2024

Language: Английский

Citations

1
Elevated serum GDF15 level as an early indicator of proximal tubular cell injury in acute kidney injury DOI

Thokozani Sawasawa,

Jiunn‐Diann Lin, Yuan‐Hung Wang

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 357, P. 123093 - 123093

Published: Oct. 1, 2024

Language: Английский

Citations

1
USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer DOI Creative Commons

Pan Chi,

Zhongdong Xie,

Hanbin Lin

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Abstract Metastasis is a major challenge for colorectal cancer (CRC) treatment. Here, we uncovered CENPF may be involved in CRC metastasis through bioinformatics mining and small interfering RNA (siRNA) targeted functional screening. We observed expression was preferentially increased tissues compared to adjacent normal tissues. More importantly, multicenter cohort study identified upregulated significantly correlated with poor survival CRC. Knockdown of inhibited cell invasion vitro vivo. Intriguingly, found undergoes degradation via the ubiquitination-proteasome pathway. Mechanistically, that USP4 interacted stabilized deubiquitination. Furthermore, USP4-mediated upregulation critical regulators Examination clinical samples confirmed positively correlates protein expression, but not mRNA transcript levels. Taken together, this describes novel USP4-CENPF signaling axis which crucial metastasis, potentially serving as therapeutic target promising prognostic biomarker

Language: Английский

Citations

0