Phosphocreatine mitigates pulmonary fibrosis in STZ-induced diabetic rats with bleomycin injury through TGF-β/Smad and Wnt/β-catenin pathways.

IF 3.1 4区 生物学 Q1 ANATOMY & MORPHOLOGY
Fu Han Wang, Abdulrahman Khaled Alwesabi, Eskandar Qaed, Waleed Aldahmash, Mueataz A Mahyoub, Marwan Almoiliqy
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引用次数: 0

Abstract

Diabetes accelerates pulmonary fibrosis through chronic inflammation, oxidative stress, and fibroblast activation. Key signaling pathways, including TGF-β/Smad and Wnt/β-catenin, drive fibroblast activation and epithelial-mesenchymal transition (EMT), contributing to lung fibrotic remodeling. This study investigated the therapeutic potential of phosphocreatine (PCr) in a combined model of STZ-induced diabetes and bleomycin-induced lung fibrosis. Histopathological changes were assessed using H&E, Masson's Trichrome, and Sirius Red staining, revealing alveolar injury, inflammatory infiltration, and collagen deposition. Mitochondrial function was evaluated by measuring ATP production and citrate synthase activity. PCr treatment markedly mitigated lung fibrosis, preserved alveolar structure, restored mitochondrial bioenergetics, and reduced inflammation and oxidative stress, likely via modulation of TGF-β/Smad and Wnt/β-catenin signaling. These findings suggest that PCr may serve as a promising multi-targeted therapeutic strategy for diabetes-associated pulmonary fibrosis.

磷酸肌酸通过TGF-β/Smad和Wnt/β-catenin通路减轻stz诱导的糖尿病博来霉素损伤大鼠肺纤维化。
糖尿病通过慢性炎症、氧化应激和成纤维细胞活化加速肺纤维化。包括TGF-β/Smad和Wnt/β-catenin在内的关键信号通路驱动成纤维细胞活化和上皮-间质转化(EMT),促进肺纤维化重塑。本研究探讨了磷酸肌酸(PCr)在stz诱导的糖尿病和博莱霉素诱导的肺纤维化联合模型中的治疗潜力。采用H&E、马氏三色和天狼星红染色评估组织病理学变化,显示肺泡损伤、炎症浸润和胶原沉积。通过测定ATP产量和柠檬酸合成酶活性来评价线粒体功能。PCr治疗可能通过调节TGF-β/Smad和Wnt/β-catenin信号通路,显著减轻肺纤维化,保存肺泡结构,恢复线粒体生物能量,减少炎症和氧化应激。这些发现表明,PCr可能作为一种有希望的多靶点治疗糖尿病相关肺纤维化的策略。
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来源期刊
Tissue & cell
Tissue & cell 医学-解剖学与形态学
CiteScore
3.90
自引率
0.00%
发文量
234
期刊介绍: Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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