PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells DOI Creative Commons
Tian Liang, Liyun Liu,

C.Y. Wang

и другие.

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Май 12, 2025

Epithelial Ovarian Cancer (EOC) is complex and heterogeneous, making accurate prognosis treatment prediction difficult. New therapeutic targets their mechanisms are urgently needed. This study explored the role of PTTG1 in ovarian cancer via cGMP-PKG signaling pathway, focusing on its effects M2 macrophage polarization EMT progression EOC cells. Using GSE135886 database, we performed differential gene expression, pathway enrichment, immune infiltration analyses to identify key influencing polarization. We then constructed knockdown overexpression cell lines assess impact proliferation, migration, invasion, EMT, vitro. Analysis revealed that differentially expressed genes were enriched correlated with macrophages. A2780 SK-OV-3 cells promoted while enhancing sGC, PKG1, PKG2 expression activate induce produced opposite results, reinforcing our conclusions. uncovers a novel mechanism development suggests it as potential target.

Язык: Английский

Exosomal Prolactin-Induced Protein Inhibits the Activation of cGMP/PKG Pathway Mediated by ATP2B2 to Promote Myocardial Fibrosis in Atrial Fibrillation DOI
Wei Yue, Xiang Li,

Zimo Sha

и другие.

Antioxidants and Redox Signaling, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Aims: Myocardial fibrosis is an important medium for atrial fibrillation (AF). Exosomes have been demonstrated to affect the development of AF. This study explored molecular mechanism exosomes from patients with AF (AF-exo) mediating myocardial and thus affecting Results: Prolactin-induced protein (PIP) highly expressed in AF-exo. AF-exo promoted proliferation activation cardiac fibroblasts (CFs) as well migration endothelial-to-mesenchymal transition (EndMT) human umbilical vein endothelial cells (HUVECs). However, effect on CFs HUVECs was mitigated by PIP-specific short hairpin RNA (shPIP). Adeno-associated virus (AAV)-shPIP reduced incidence duration rats, improved collagen deposition. ATPase plasma membrane Ca2+ transporting 2 (ATP2B2) overexpression or inhibition reverses role PIP shPIP CFs, HUVECs, rats. Activation cyclic guanosine monophosphate/protein kinase G (cGMP/PKG) pathway beneficial alleviate fibrosis, but this shATP2B2. Innovation: Our investigation substantiates pivotal PIP/ATP2B2 axis both HUVEC EndMT progression. findings suggest that can suppress cGMP/PKG mediated ATP2B2 through exosomal PIP, promoting indicating potential targets novel antifibrotic drug targeting either ATP2B2. Conclusion: Exosomal inhibit ATP2B2, Antioxid. Redox Signal. 00, 000-000.

Язык: Английский

Процитировано

0

Exercise and tissue fibrosis: recent advances in therapeutic potential and molecular mechanisms DOI Creative Commons
Zheng Zhao, Yongxue Zhu, David Wan

и другие.

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Март 20, 2025

Tissue fibrosis represents an aberrant repair process, occurring because of prolonged injury, sustained inflammatory response, or metabolic disorders. It is characterized by excessive accumulation extracellular matrix (ECM), resulting in tissue hardening, structural remodeling, and loss function. This pathological phenomenon a common feature the end stage numerous chronic diseases. Despite advent novel therapeutic modalities, including antifibrotic agents, these have only modest efficacy reversing established are associated with adverse effects. In recent years, growing body research has demonstrated that exercise significant benefits potential treatment fibrosis. The anti-fibrotic effects mediated multiple mechanisms, direct inhibition fibroblast activation, reduction expression pro-fibrotic factors such as transforming growth factor-β (TGF-β) slowing collagen deposition. Furthermore, been to assist maintaining dynamic equilibrium repair, thereby indirectly reducing damage can also help maintain balance improving disorders, exerting anti-inflammatory antioxidant effects, regulating cellular autophagy, restoring mitochondrial function, activating stem cell activity, apoptosis, alleviating tissue. paper presents review its underlying mechanisms for range fibrosis, cardiac, pulmonary, renal, hepatic, skeletal muscle. offers valuable reference point non-pharmacological intervention strategies comprehensive fibrotic

Язык: Английский

Процитировано

0

Cardiac Fibrosis in the Multi-Omics Era: Implications for Heart Failure DOI Creative Commons
Rachad Ghazal, Min Wang, Duan Liu

и другие.

Circulation Research, Год журнала: 2025, Номер 136(7), С. 773 - 802

Опубликована: Март 27, 2025

Cardiac fibrosis, a hallmark of heart failure and various cardiomyopathies, represents complex pathological process that has long challenged therapeutic intervention. High-throughput omics technologies have begun revolutionizing our understanding the molecular mechanisms driving cardiac fibrosis are providing unprecedented insights into its heterogeneity progression. This review provides comprehensive analysis how techniques—encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics—are insight fibrosis. Genomic studies identified novel genetic variants regulatory networks associated with susceptibility progression, single-cell transcriptomics unveiled distinct fibroblast subpopulations unique signatures. Epigenomic profiling revealed dynamic chromatin modifications controlling activation states, proteomic analyses biomarkers potential targets. Metabolomic uncovered important alterations in energetics substrate utilization during fibrotic remodeling. The integration these multi-omic data sets led to identification previously unrecognized pathogenic targets, including cell-type-specific interventions metabolic modulators. We discuss advances development precision medicine approaches for while highlighting current challenges future directions translating effective strategies. systems-level perspective on may inform more effective, personalized related cardiovascular diseases.

Язык: Английский

Процитировано

0

The immunology of diabetic cardiomyopathy DOI Creative Commons

Ming Song,

Honggang Dai,

Quan Zhou

и другие.

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Апрель 7, 2025

Diabetic cardiomyopathy is a notable microvascular complication of diabetes, characterized primarily by myocardial fibrosis and functional abnormalities. Long-term hyperglycemia induces excessive activation recruitment immune cells triggers the cascade inflammatory responses, resulting in systemic local cardiac inflammation. Emerging evidence highlights significant roles immunology modulating pathology diabetic cardiomyopathy. As primary effectors reactions, are consistently present tissue can be recruited under pathological circumstances. A disproportionate favor to proinflammatory types increased cytokine levels mediate fibroblast proliferation, phenotypic transformation, collagen synthesis ultimately rise hypertrophy. Meanwhile, severity also strongly associated with diverse phenotypes alterations cells, including macrophages, dendritic mast neutrophils, natural killer innate immunity CD4+ T lymphocytes, CD8+ B lymphocytes adaptive immunity. In this review, we synthesized current analysis critical role played system its components progression Finally, highlight preclinical clinical targeting strategies translational implications.

Язык: Английский

Процитировано

0

PTTG1 promotes M2 macrophage polarization via the cGMP-PKG signaling pathway and facilitates EMT progression in human epithelial ovarian cancer cells DOI Creative Commons
Tian Liang, Liyun Liu,

C.Y. Wang

и другие.

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Май 12, 2025

Epithelial Ovarian Cancer (EOC) is complex and heterogeneous, making accurate prognosis treatment prediction difficult. New therapeutic targets their mechanisms are urgently needed. This study explored the role of PTTG1 in ovarian cancer via cGMP-PKG signaling pathway, focusing on its effects M2 macrophage polarization EMT progression EOC cells. Using GSE135886 database, we performed differential gene expression, pathway enrichment, immune infiltration analyses to identify key influencing polarization. We then constructed knockdown overexpression cell lines assess impact proliferation, migration, invasion, EMT, vitro. Analysis revealed that differentially expressed genes were enriched correlated with macrophages. A2780 SK-OV-3 cells promoted while enhancing sGC, PKG1, PKG2 expression activate induce produced opposite results, reinforcing our conclusions. uncovers a novel mechanism development suggests it as potential target.

Язык: Английский

Процитировано

0