Ganggang Li , Yuzhi Huo , Xiaochuan Pan , Nan Jia , Xuanyu Wu , Xinhui Wu , Fei Wang , Quanyu Du
{"title":"靶向免疫代谢界面:IPF治疗的新策略","authors":"Ganggang Li , Yuzhi Huo , Xiaochuan Pan , Nan Jia , Xuanyu Wu , Xinhui Wu , Fei Wang , Quanyu Du","doi":"10.1016/j.pupt.2025.102394","DOIUrl":null,"url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by aberrant tissue remodeling and excessive deposition of extracellular matrix components. Emerging evidence underscores the critical role of the immunometabolism in the pathogenesis of IPF, highlighting how dysregulated metabolic pathways modulate immune responses and contribute to fibrotic progression. Key molecular regulators such as <em>PPARG</em> (<em>peroxisome proliferator activated receptor gamma</em>) and <em>SPP1</em> (<em>secreted phosphoprotein 1</em>), along with signaling pathways including mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and <em>hypoxia-inducible factor 1-alpha (HIF-1α)</em>, orchestrate immune cell polarization, fibroblast activation, and extracellular matrix production. These insights reveal promising therapeutic targets at the intersection of metabolism and immunity. This review synthesizes current findings on immunometabolism interactions in IPF, emphasizing the potential of metabolic reprogramming and immune modulation as novel treatment strategies. Despite substantial advances, significant challenges persist in elucidating the precise mechanisms underlying these interactions and translating preclinical insights into effective clinical interventions. Future research should prioritize the identification of actionable metabolic biomarkers, refinement of molecular targets, and development of personalized therapeutic approaches. Addressing these gaps may pave the way for innovative therapies capable of halting or even reversing fibrosis, ultimately improving outcomes for patients with IPF.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"91 ","pages":"Article 102394"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Targeting the immunometabolism interface: A novel strategy for IPF therapy\",\"authors\":\"Ganggang Li , Yuzhi Huo , Xiaochuan Pan , Nan Jia , Xuanyu Wu , Xinhui Wu , Fei Wang , Quanyu Du\",\"doi\":\"10.1016/j.pupt.2025.102394\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by aberrant tissue remodeling and excessive deposition of extracellular matrix components. Emerging evidence underscores the critical role of the immunometabolism in the pathogenesis of IPF, highlighting how dysregulated metabolic pathways modulate immune responses and contribute to fibrotic progression. Key molecular regulators such as <em>PPARG</em> (<em>peroxisome proliferator activated receptor gamma</em>) and <em>SPP1</em> (<em>secreted phosphoprotein 1</em>), along with signaling pathways including mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and <em>hypoxia-inducible factor 1-alpha (HIF-1α)</em>, orchestrate immune cell polarization, fibroblast activation, and extracellular matrix production. These insights reveal promising therapeutic targets at the intersection of metabolism and immunity. This review synthesizes current findings on immunometabolism interactions in IPF, emphasizing the potential of metabolic reprogramming and immune modulation as novel treatment strategies. Despite substantial advances, significant challenges persist in elucidating the precise mechanisms underlying these interactions and translating preclinical insights into effective clinical interventions. Future research should prioritize the identification of actionable metabolic biomarkers, refinement of molecular targets, and development of personalized therapeutic approaches. Addressing these gaps may pave the way for innovative therapies capable of halting or even reversing fibrosis, ultimately improving outcomes for patients with IPF.</div></div>\",\"PeriodicalId\":20799,\"journal\":{\"name\":\"Pulmonary pharmacology & therapeutics\",\"volume\":\"91 \",\"pages\":\"Article 102394\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pulmonary pharmacology & therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1094553925000513\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pulmonary pharmacology & therapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1094553925000513","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Targeting the immunometabolism interface: A novel strategy for IPF therapy
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by aberrant tissue remodeling and excessive deposition of extracellular matrix components. Emerging evidence underscores the critical role of the immunometabolism in the pathogenesis of IPF, highlighting how dysregulated metabolic pathways modulate immune responses and contribute to fibrotic progression. Key molecular regulators such as PPARG (peroxisome proliferator activated receptor gamma) and SPP1 (secreted phosphoprotein 1), along with signaling pathways including mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and hypoxia-inducible factor 1-alpha (HIF-1α), orchestrate immune cell polarization, fibroblast activation, and extracellular matrix production. These insights reveal promising therapeutic targets at the intersection of metabolism and immunity. This review synthesizes current findings on immunometabolism interactions in IPF, emphasizing the potential of metabolic reprogramming and immune modulation as novel treatment strategies. Despite substantial advances, significant challenges persist in elucidating the precise mechanisms underlying these interactions and translating preclinical insights into effective clinical interventions. Future research should prioritize the identification of actionable metabolic biomarkers, refinement of molecular targets, and development of personalized therapeutic approaches. Addressing these gaps may pave the way for innovative therapies capable of halting or even reversing fibrosis, ultimately improving outcomes for patients with IPF.
期刊介绍:
Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews.
Research Areas Include:
• All major diseases of the lung
• Physiology
• Pathology
• Drug delivery
• Metabolism
• Pulmonary Toxicology.