Hedgehog-interacting protein orchestrates alveologenesis and protects against bronchopulmonary dysplasia and emphysema
文献类型：期刊论文
| 作者 | Ye, Datian9; Feng, Shiyun8; Yang, Xinguo7; Su, Yanjing9; Zhang, Jing6; Feng, Haixin5,9; Zhou, Minqi4; Zhou, Bin2,3; Duan, Lihui3,5; Peng, Tien4 |
| 刊名 | SCIENCE ADVANCES
 |
| 出版日期 | 2025-05-07 |
| 卷号 | 11期号:19页码:17 |
| ISSN号 | 2375-2548 |
| DOI | 10.1126/sciadv.adu2958 |
| 英文摘要 | Most of the lung's gas-exchange surface forms during alveologenesis and its disruption causes bronchopulmonary dysplasia (BPD) in infants, characterized by alveolar simplification and myofibroblast accumulation. BPD also increases the risk of adult emphysema, marked by alveolar loss. Despite this connection, mechanisms linking these conditions and effective treatments are still lacking. We identify hedgehog-interacting protein (HHIP), associated with both BPD and emphysema, as a critical regulator of alveologenesis. During this process, Hhip-expressing cells expanded, accompanied by hedgehog (Hh) signaling inhibition and myofibroblast transition. Stromal-specific Hhip deletion led to hyperactivation of Hh-IGF1 signaling axis, causing persistent SMA+ myofibroblasts and epithelial stem/progenitor cell senescence. Hyperactivation of this pathway was also observed in human BPD and hyperoxia-induced BPD models. Early Hhip deficiency resulted in adult emphysema with myofibroblast accumulation. We developed a therapeutic Fc-fused HHIP protein that mitigated BPD in neonatal mice and prevented adult emphysema. These findings establish HHIP as a critical regulator of alveologenesis and a therapeutic target for BPD and emphysema. |
| WOS关键词 | GENOME-WIDE ASSOCIATION ; GROWTH-FACTOR-I ; SONIC-HEDGEHOG ; LIFE-SPAN ; LUNG ; RECEPTOR ; IGF-1 ; EXPRESSION ; CELLS ; ALVEOLARIZATION |
| 资助项目 | National Natural Science Foundation of China[82370070] ; National Key R&D Program of China[2024YFA1107703] ; Major Project of Guangzhou National Laboratory[GZNL2023A01003] ; Shanghai Pujiang Program[22PJ1415700] ; Guangdong Basic and Applied Basic Research Foundation[2023A1515012459] ; Zhongshan Science and Technology Bureau[CXTD2023009] ; Guangdong Province High-level Innovative Research Institute[2021B0909050003] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001483895900023 |
| 出版者 | AMER ASSOC ADVANCEMENT SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317857]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Wang, Chaoqun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, New Cornerstone Sci Lab, Key Lab Multicell Syst,Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA 5.Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 7.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China 8.Perfect GuangDong Co Ltd, Perfect Life Sci Res Inst, Zhongshan 528402, Peoples R China 9.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ye, Datian,Feng, Shiyun,Yang, Xinguo,et al. Hedgehog-interacting protein orchestrates alveologenesis and protects against bronchopulmonary dysplasia and emphysema[J]. SCIENCE ADVANCES,2025,11(19):17. |
| APA | Ye, Datian.,Feng, Shiyun.,Yang, Xinguo.,Su, Yanjing.,Zhang, Jing.,...&Wang, Chaoqun.(2025).Hedgehog-interacting protein orchestrates alveologenesis and protects against bronchopulmonary dysplasia and emphysema.SCIENCE ADVANCES,11(19),17. |
| MLA | Ye, Datian,et al."Hedgehog-interacting protein orchestrates alveologenesis and protects against bronchopulmonary dysplasia and emphysema".SCIENCE ADVANCES 11.19(2025):17. |
入库方式： OAI收割
来源：上海药物研究所
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