以瘢痕挛缩型为主的良性气道狭窄，呼吸内镜介入疗效差。探讨调控上游始动因子维持成纤维细胞稳态，控制气道狭窄瘢痕化的进程是重要的科学问题。申请人前期研究发现，瘢痕挛缩型气道狭窄患者血清载脂蛋白A-I（ApoA-I）水平降低，且人原代气道肉芽成纤维细胞高表达ApoA-I的转运子ABCA1。预实验提示ABCA1介导ApoA-I发挥了抑制成纤维细胞增殖、迁移及产生肌成纤维细胞表型等功能，并初步发现ApoA-I模拟肽D-4F对cGAS-STING通路具有抑制作用。本项目拟结合CRISPR-Cas9基因编辑、RNA sequence等技术，从临床样本、细胞、动物模型等水平阐明ApoA-I模拟肽D-4F通过负调控cGAS-STING通路影响成纤维细胞功能的具体机制，明确经呼吸内镜下腔内注射ApoA-I模拟肽抑制气道肉芽瘢痕增生的疗效。本项目有助于为介入肺脏病学创新诊疗技术的理论丰富和应用开拓提供新线索。

Patients with keloid phenotype benign airway stenosis has poor curative effect after endoscopic interventional therapy. It is an important scientific issue to explore the regulation of upstream initiating factors to maintain fibroblast homeostasis and control the process of airway scarring. Previous studies by our team showed that serum apolipoprotein (ApoA-I) level was reduced in patients with keloid phenotype benign airway stenosis. The transporter of ApoA-I named ABCA1 was highly expressed in human primary airway granulation fibroblasts.Our experiments suggested that ABCA1 mediated ApoA-I played a role in inhibiting fibroblast proliferation, migration and producing myofibroblast phenotype. It was preliminarily found that Apolipoprotein A-I mimics peptide D-4F had an inhibitory effect on cGAS-STING pathway.This project aims to systematically explore the molecular mechanism of Apolipoprotein A-I mimics peptide D-4F affecting the function of fibroblasts by negative regulating the cGAS-STING pathway in clinical samples, cells and animal models through the technologies of CRISPR-Cas9 gene knockout and RNA sequence. This project also intends to illustrate the potential efficacy of local injection of D-4F in the treatment of airway stenosis through respiratory endoscopy. The results will provide a new clue for the theoretical enrichment and innovative application in the interventional pulmonary medicine.