Details

Autor(en) / Beteiligte

• Deng, Jing
• Wei, Rui-Qi
• Zhang, Wen-Mei
• Shi, Chang-Yu
• Yang, Rui
• Jin, Ming
• Piao, Chunmei

Titel

Crocin's role in modulating MMP2/TIMP1 and mitigating hypoxia-induced pulmonary hypertension in mice

Ist Teil von

• Scientific reports, 2024-06, Vol.14 (1), p.12716, Article 12716

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Abstract To explore the molecular pathogenesis of pulmonary arterial hypertension (PAH) and identify potential therapeutic targets, we performed transcriptome sequencing of lung tissue from mice with hypoxia-induced pulmonary hypertension. Our Gene Ontology analysis revealed that “extracellular matrix organization” ranked high in the biological process category, and matrix metallopeptidases (MMPs) and other proteases also played important roles in it. Moreover, compared with those in the normoxia group, we confirmed that MMP s expression was upregulated in the hypoxia group, while the hub gene Timp1 was downregulated. Crocin, a natural MMP inhibitor, was found to reduce inflammation, decrease MMPs levels, increase Timp1 expression levels, and attenuate hypoxia-induced pulmonary hypertension in mice. In addition, analysis of the cell distribution of MMPs and Timp1 in the human lung cell atlas using single-cell RNAseq datasets revealed that MMPs and Timp1 are mainly expressed in a population of fibroblasts. Moreover, in vitro experiments revealed that crocin significantly inhibited myofibroblast proliferation, migration, and extracellular matrix deposition. Furthermore, we demonstrated that crocin inhibited TGF-β1-induced fibroblast activation and regulated the pulmonary arterial fibroblast MMP2/TIMP1 balance by inhibiting the TGF-β1/Smad3 signaling pathway. In summary, our results indicate that crocin attenuates hypoxia-induced pulmonary hypertension in mice by inhibiting TGF-β1-induced myofibroblast activation.