FP 受体通过 PI3K/AKT/mTOR 信号通路抑制自噬，加重与衰老相关的心脏纤维化

IF 3.8 3区医学 Q2 GERIATRICS & GERONTOLOGY

Archives of gerontology and geriatrics Pub Date : 2025-03-08 DOI:10.1016/j.archger.2025.105824

Jia Qi , Bin Lu , Cheng-wei Jin , Yuan-yuan Shang , Hui Pan , Hao Li , Zhou-jie Tong , Wei Zhang , Lu Han , Ming Zhong

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引用次数: 0

摘要

f -前列腺素受体（FP受体）是前列腺素F2α(PGF2α)的受体，参与组织纤维化过程，但其在心脏衰老中的确切作用尚不清楚。方法采用基因沉默的方法对不同组小鼠心功能、心肌纤维化水平、自噬水平及相关机制通路进行研究。在细胞水平上，我们模拟了心脏成纤维细胞的衰老过程，并利用相关抑制剂研究了相关机制。结果衰老小鼠FP受体和PI3K/AKT/mTOR通路增加，自噬水平降低，最终导致心肌纤维化。FP受体基因沉默减缓了上述过程。我们在细胞水平上发现了类似的变化。结论fp受体可激活PI3K/AKT/mTOR通路，抑制心肌自噬，导致衰老相关性心肌纤维化。因此，抑制FP受体可以改善与衰老相关的心脏重塑，暗示其潜在的治疗应用于治疗与衰老相关的心血管疾病。

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FP receptor inhibits autophagy to aggravate aging-related cardiac fibrosis through PI3K/AKT/mTOR signaling pathway

Background

F-prostanoid receptor (FP receptor), a receptor for Prostaglandin F2α(PGF2α), is involved in the process of tissue fibrosis, but its exact role in the aging heart remains unclear.

Methods

We investigated cardiac function, myocardial fibrosis levels, autophagy levels and related mechanistic pathways in different groups of mice using gene silencing. At the cellular level, we simulated the senescence process of cardiac fibroblasts and investigated the related mechanisms using relevant inhibitors.

Results

In aging mice, FP receptor and PI3K/AKT/mTOR pathways are increased and autophagy levels are decreased, ultimately leading to cardiac fibrosis. FP receptor gene silencing slows down the above process. We found similar changes at the cellular level.

Conclusion

FP receptor could activate PI3K/AKT/mTOR pathway and inhibit cardiac autophagy, which resulted in aging-related cardiac fibrosis. Thus, the inhibition of FP receptor could improve aging-related cardiac remodeling, implicating its potential therapeutic application to treat cardiovascular diseases associated with aging.

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来源期刊

Archives of gerontology and geriatrics 医学-老年医学

CiteScore

7.30

自引率

5.00%

发文量

198

审稿时长

16 days

期刊介绍： Archives of Gerontology and Geriatrics provides a medium for the publication of papers from the fields of experimental gerontology and clinical and social geriatrics. The principal aim of the journal is to facilitate the exchange of information between specialists in these three fields of gerontological research. Experimental papers dealing with the basic mechanisms of aging at molecular, cellular, tissue or organ levels will be published. Clinical papers will be accepted if they provide sufficiently new information or are of fundamental importance for the knowledge of human aging. Purely descriptive clinical papers will be accepted only if the results permit further interpretation. Papers dealing with anti-aging pharmacological preparations in humans are welcome. Papers on the social aspects of geriatrics will be accepted if they are of general interest regarding the epidemiology of aging and the efficiency and working methods of the social organizations for the health care of the elderly.