The pivotal role of human endometrial stromal cells (hESCs) in the development of endometriosis lies in their ability to adopt a pro-invasive and proinflammatory profile upon migration to areas outside the uterus. However, the molecular mechanisms involved in these events remain unclear. In this study, we investigated how angiotensin II (Ang II) affects the plasminogen-plasmin system in hESCs, and the mechanisms underlying cell proliferation, migration, matrix degradation, and inflammation. Precursors, receptors, and peptidases involved in angiotensin metabolism increased significantly in Ang II-treated hESCs. The expression and activity of tissue (tPA)- and urokinase (uPA)- type plasminogen activators and the receptor for uPA (uPAR) were induced in the presence of Ang II. The up-regulation of tPA-uPA/uPAR pathway significantly contributes to heightened plasmin production both on the surface of hESCs and in their conditioned media. As a result, the plasmin generation induced by Ang II enhances the degradation of fibrin and matrix proteins, while also boosting hESC viability, proliferation, and migration through the up-regulation of growth factor expression. Notably, Ang II-induced hESC migration was dependent on the generation of active plasmin on cell surface. Ang II regulates oxidative and inflammatory signalling in hESCs primarily via NADPH oxidase and through the up-regulation of proinflammatory cytokines and adhesion molecules. Interestingly, Ang II receptor (AT1R) blockage, decreased plasmin generation, tPA-uPA/uPAR expression and hESC migration. Our results suggest that Ang II/AT1R axis regulates hESC proliferation and migration through tPA-uPA/uPAR pathway activation and plasmin generation. We propose the Ang II/AT1R axis as a potential target for endometriosis treatment.
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http://dx.doi.org/10.1016/j.bcp.2024.116280 | DOI Listing |
World J Urol
January 2025
Department of Urology, Peking University People's Hospital, Beijing, 100044, China.
Purpose: This study aims to elucidate the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in Hunner-type Interstitial Cystitis (HIC) and evaluate its potential as a therapeutic target.
Methods: Bladder tissue samples were obtained from HIC patients and normal bladder tissue from bladder cancer patients. PACAP expression was assessed through immunohistochemistry.
Cell Death Discov
January 2025
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Metabolic reprogramming is considered one of the hallmarks of cancer in which cancer cells reprogram some of their metabolic cascades, mostly driven by the specific chemical microenvironment in cancer tissues. The altered metabolic pathways are increasingly being considered as potential targets for cancer therapy. In this view, Aldolase A (ALDOA), a key glycolytic enzyme, has been validated as a candidate oncogene in several cancers.
View Article and Find Full Text PDFSci Rep
January 2025
Prenatal Diagnosis Center in Guizhou Province, The Affiliated Hospital of Guizhou Medical University, Guizhou, Guiyang, 550009, China.
Cervical cancer (CESC) presents significant clinical challenges due to its complex tumor microenvironment (TME) and varied treatment responses. This study identified undifferentiated M0 macrophages as high-risk immune cells critically involved in CESC progression. Co-culture experiments further demonstrated that M0 macrophages significantly promoted HeLa cell proliferation, migration, and invasion, underscoring their pivotal role in modulating tumor cell behavior within the TME.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
School of Pharmacy, Qingdao University, Qingdao 266071, China. Electronic address:
Complex wound closure scenarios necessitate the development of advanced wound dressings that can effectively address the challenges of filling irregularly shaped wounds and managing fatigue failures encountered in daily patient activities. To tackle these issues, we develop a multifunctional hydrogel from natural polysaccharides and polypeptides with injectability and self-healing properties for promoting full-time and multipurpose wound healing. Synthesized through dynamic Schiff base linkages between oxidized hyaluronic acid (OHA), ε-polylysine (ε-PL), and quaternized chitosan (QCS), the OHA/ε-PL/QCS hydrogel can gel rapidly within 50 s.
View Article and Find Full Text PDFPeptides
January 2025
University of Tunis El Manar, Faculty of Sciences of Tunis, LR18ES03 Laboratory of Neurophysiology, Cellular Physiopathology and Biomolecules Valorisation. 2092 Tunis, Tunisia.
Migration is an essential characteristic of cells that occurs during many physiological and pathological processes. Astrocytes represent the most abundant cell type in the adult central nervous system (CNS), that play a crucial role in various functions such as guiding and supporting neuronal migration during development and maintaining brain homeostasis at adulthood. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN).
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