PARP7 protects the lung epithelial barrier from diverse environmental threats

• 成果类型: Article
• 署名作者: Jeltema, Devon; Yang, Kun; Baty, Joshua J.; Araszkiewicz, Antonina; Xing, Cong; Knox, Kennady; Tang, Zhen; Dobbs, Nicole; Yan, Nan
• 署名单位: University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2525274123
• 发表日期: 2026-03-10
• 页码: e2525274123
• 关键词: PARP7; lung epithelial barrier; autoimmunity; lupus; air-liquid interface; DIFFUSE ALVEOLAR HEMORRHAGE; i interferon; PRISTANE; tiparp; cells; mice

摘要

Poly-ADP-ribose polymerase (PARP) family proteins are involved in a wide range of cellular processes. Several PARPs are targeted by inhibitors as treatments for cancer based on their biochemical functions; however, the physiological functions of most PARPs and the potential adverse effects of PARP inhibition are unknown. Here, we show that PARP7 is important for lung physiology. Loss of PARP7 in mice increases susceptibility to chemically induced diffuse alveolar hemorrhaging (DAH) and pristane-induced lupus. Single-nucleus RNA-seq reveals that PARP7 is selectively expressed in alveolar type I cells and PARP7 loss increases immune cell infiltration within the lung, indicating a loss of epithelial barrier integrity. Further, leads to increased barrier permeability after cigarette smoke challenge or bacterial olizing genes and proinflammatory genes. Together, our study uncovers PARP7 as a key player in maintaining the epithelial barrier integrity within the lung, which may have important implications for pulmonary diseases and for guiding PARP7 inhibitor use in the clinic.