CXCL14 Accelerates Fibroblast Ferroptosis in Inflammatory Bowel Disease by Regulating Lipid Metabolism via SCD1 DOI Creative Commons

Zhihua HE,

Lan Lin,

Chen Nini

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 18, 2023

Abstract Inflammatory bowel disease (IBD), historically subdivided into Crohn’s and ulcerative colitis, is a chronic, relapsing heterogeneous condition, resulting in intestinal tissue destruction dysfunction, such as fibrosis. Currently, there no effective therapy against colon Fibroblasts are known to contribute the pathogenesis of IBD-related Recently, our laboratory found that inflammatory fibroblasts IBD had significantly upregulated Chemokine (C-X-C motif) ligand 14 (CXCL14) expression, suggesting potential role CXCL14 Employing Dextran sodium sulfate(DSS)-induced chronic we showed was specifically collagen-secreting fibrotic mouse colons. In addition, human fibroblast (HIF CCD18) culture supernatants induced by transforming growth factor-β1 (TGF-β1), whereas overexpression sufficient promote ferroptosis. Mechanistically, CXCL14, transcriptionally decreasing transcript abundance stearoyl-CoA desaturase-1 (SCD1), mediated its pro-ferroptosis effects enforcing ERK signaling activity inhibiting p70 KDa ribosomal protein S6 kinase (S6K) activation fibroblasts. Using S100 calcium binding A4 (S100a4)-cre mice, generated an fibroblast-specific knockout line through Adeno-associated virus vectors (AAV) injection tail veins. We demonstrated deletion accelerated progression established fibrosis dextran sulfate (DSS)-induced therapeutic targeting for IBD.

Language: Английский

S-RBD-modified and miR-486-5p-engineered exosomes derived from mesenchymal stem cells alleviate radiation-induced lung injury and long-term pulmonary fibrosis via suppression of ferroptosis DOI Creative Commons

Weiyuan Zhang,

Wen Li, Li Du

et al.

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

Published: Feb. 6, 2024

Abstract Background Radiation-induced pulmonary fibrosis (RIPF) is a late-stage complication of therapeutic radiation, associated with poor prognosis and limited options. lung injury (RILI) an early manifestation RIPF, intervention RILI effective method for preventing long-term RIPF. Mesenchymal stem cell (MSC)-derived exosomes exhibit regenerative activity in injured lungs are drug-delivery nanoparticles. SARS-CoV-2-S-RBD enables ACE2 + targeting MSC extracellular vesicles. miR-486-5p multifunctional miRNA angiogenic anti-fibrotic activities enriched MSC-derived exosomes. In this study, we investigated the effects SARS-COV-2-S-RBD-engineered on RIPF vitro vivo . Results Adenovirus-mediated gene modification led to overexpression umbilical cord MSCs (UC-MSCs), which further UC-MSCs-derived MiR-486-5p-engineered (miR-486-MSC-Exo) promoted proliferation migration irradiated MLE-12 cells inhibited An assay revealed occurrence ferroptosis, major form death during radiation injury, indicated by upregulated expression fibrosis-related genes. miR-486-MSC-Exo effectively reversed these changes. MiR-486-MSC-Exo strongly genes induced TGF improved pathological model The distribution RBD-VSVG-MSC labeled DiR dye hACE2 CKI/CKI Sftpc-Cre mice demonstrated that fluorescence RBD-VSVG remained long time. miR-486-RBD-MSC-exosomes significantly survival rate changes mice. Furthermore, exerted through targeted inhibition SMAD2 activation Akt phosphorylation. Conclusions Here, alleviated Surface COVID-S-RBD conferred engineered ability target animal models. COVID-S-RBD-engineered were enhanced. modified recombinant enabled delivery miR-486-5p, approach treatment

Language: Английский

Citations

0
Human umbilical cord mesenchymal stem cells restore chemotherapy-induced premature ovarian failure by inhibiting ferroptosis in vitro ovarian culture system DOI Creative Commons
Jiaqi Chen,

Zhuoying He,

Wenjuan Xu

et al.

Reproductive Biology and Endocrinology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 7, 2024

Mesenchymal stem cells (MSCs) have shown potential in repairing chemotherapy-induced premature ovarian failure (POF). However, challenges such as cell loss and immune phagocytosis post-transplantation hinder their application. Due to easy safe handling, vitro culture is widely available for drug screening, pathophysiological research, fertilization. MSCs could exhibit therapeutic capacity injury, avoid tissue system. Therefore, this study utilizes an system investigate the reparative of human umbilical cord mesenchymal (hUCMSCs) mechanism.

Language: Английский

Citations

0
Focus on the Role of Inflammation as a Bridge between Ferroptosis and Atrial Fibrillation: A Narrative Review and Novel Perspective DOI Creative Commons

C. Jin,

Z. Zhong,

Longzhe Gao

et al.

Reviews in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 25(4), P. 110 - 110

Published: March 25, 2024

In this comprehensive review, we examine the intricate interplay between inflammation, ferroptosis, and atrial fibrillation (AF), highlighting their significant roles in AF pathophysiology pathogenesis. Augmented inflammatory responses are pivotal to AF, potentially leading remodeling reentry phenomena by impacting calcium channels tissue fibrosis. A strong correlation exists cytokines underscoring importance of signaling pathways, such as NOD-like receptor thermal protien domain associated protein 3 (NLRP3) inflammasome, Nuclear Factor kappa B (NF-

Language: Английский

Citations

0
Ferroptosis: A New Strategy for the Treatment of Fibrotic Diseases DOI Open Access

Zhuo Pei,

Jing Fan,

Maolin Tang

et al.

Advanced Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 8, 2024

Abstract Ferroptosis is a new type of cell death characterized by iron dependence and the excessive accumulation lipid reactive oxygen species (lipid ROS) that has gradually become better characterized. There sufficient evidence indicating ferroptosis associated with variety human life activities diseases, such as tumor suppression, ischemic organ injury, degenerative disorders. Notably, also involved in initiation development fibrosis various organs, including liver fibrosis, pulmonary renal cardiac which usually irreversible refractory. Although large number patients urgently need to be treated, current treatment options are still limited unsatisfactory. Organ involves series complex orderly processes, parenchymal damage, recruitment inflammatory cells activation fibroblasts, ultimately leads extracellular matrix (ECM) formation fibrosis. An increasing studies have confirmed close association between these pathological processes ferroptosis. This review summarizes role function proposes several potential therapeutic strategies pathways based on

Language: Английский

Citations

0
CXCL14 Accelerates Fibroblast Ferroptosis in Inflammatory Bowel Disease by Regulating Lipid Metabolism via SCD1 DOI Creative Commons

Zhihua HE,

Lan Lin,

Chen Nini

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 18, 2023

Abstract Inflammatory bowel disease (IBD), historically subdivided into Crohn’s and ulcerative colitis, is a chronic, relapsing heterogeneous condition, resulting in intestinal tissue destruction dysfunction, such as fibrosis. Currently, there no effective therapy against colon Fibroblasts are known to contribute the pathogenesis of IBD-related Recently, our laboratory found that inflammatory fibroblasts IBD had significantly upregulated Chemokine (C-X-C motif) ligand 14 (CXCL14) expression, suggesting potential role CXCL14 Employing Dextran sodium sulfate(DSS)-induced chronic we showed was specifically collagen-secreting fibrotic mouse colons. In addition, human fibroblast (HIF CCD18) culture supernatants induced by transforming growth factor-β1 (TGF-β1), whereas overexpression sufficient promote ferroptosis. Mechanistically, CXCL14, transcriptionally decreasing transcript abundance stearoyl-CoA desaturase-1 (SCD1), mediated its pro-ferroptosis effects enforcing ERK signaling activity inhibiting p70 KDa ribosomal protein S6 kinase (S6K) activation fibroblasts. Using S100 calcium binding A4 (S100a4)-cre mice, generated an fibroblast-specific knockout line through Adeno-associated virus vectors (AAV) injection tail veins. We demonstrated deletion accelerated progression established fibrosis dextran sulfate (DSS)-induced therapeutic targeting for IBD.

Language: Английский

Citations

0