目的系统评价PAI-1基因多态性与不明原因复发性流产易感性关联,为临床提供循证医学证据。方法检索知网、万方、维普中文数据库和PubMed、Embase、Web of Science英文数据库。检索时间为建库到2024年6月。筛选文献、提取数据、质量评价后...目的系统评价PAI-1基因多态性与不明原因复发性流产易感性关联,为临床提供循证医学证据。方法检索知网、万方、维普中文数据库和PubMed、Embase、Web of Science英文数据库。检索时间为建库到2024年6月。筛选文献、提取数据、质量评价后,使用Revman软件进行Meta分析。结果最终纳入18篇文献,包括URSA组2372例,对照组2165例。Meta分析结果显示:在总体研究中:PAI-14G/5G基因多态性与URSA患病风险增加具有相关性。等位基因4G发生URSA风险高于5G等位基因[OR=1.58,95%CI(1.29-1.93)];携带4G/4G基因型、4G/5G基因型发生URSA风险高于携带5G/5G女性[4G/4G vs.5G/5G:OR=2.52,95%CI(1.67-3.80);4G/4G vs.4G/5G+5G/5G:OR=1.87,95%CI(1.38-2.54);4G/5G+4G/4G vs.5G/5G:OR=1.73,95%CI(1.34-2.24),4G/5G vs.5G/5G:OR=1.44,95%CI(1.24-1.67)]。按照地区进行亚组分析,结果仍提示PAI-14G/5G基因多态性与中国人群和非中国人群URSA存在关联。结论PAI-14G/5G基因多态性与URSA相关,携带4G/4G或4G/5G基因的女性URSA发病风险增高,进行早期干预治疗,可降低原因不明复发性流产的发生率,改善妊娠结局。展开更多
Pulmonary fibrosis(PF)is a lethal lung disease that predominantly affects older adults;however,whether and how aging triggers fibrosis remains unclear.To pinpoint the predominant initiating factors of PF,we first anal...Pulmonary fibrosis(PF)is a lethal lung disease that predominantly affects older adults;however,whether and how aging triggers fibrosis remains unclear.To pinpoint the predominant initiating factors of PF,we first analyzed single-cell RNA sequencing(scRNA-seq)data from the lung tissues of 45 normal donors and 51 PF patients and found that aging might serve as the primary catalyst for PF development.To further investigate the influence of aging on PF formation,we conducted a comprehensive and thorough study employing a natural aging mouse model.We found that dynamic alterations in the quantity and types of collagen fibers during aging-induced PF progression,especially in collagenous(Col)I,emerged as the predominant driver of PF.We then investigated the regulation of Col I synthesis during aging using primary alveolar type 2(AT2)cells and A549 cells line through conditioned media and Transwell cocul-ture,and found that secretions—particularly plasminogen activator inhibitor(PAI)-1—from aged AT2 cells promoted fibrosis and enhanced collagen type I alpha 1(Col1al)production via the transforming growth factor(TGF)-b/small mother against decapentaplegic(Smad)2/3 pathway.Furthermore,scRNA-seq and a histological analysis of human lung tissue demonstrated a significant upregulation of SERPINE1(the gene encoding PAI-1)and PAI-1 expression in both aging lung tissue and AT2 cells,which was consistent with our findings from animal experiments,providing additional evidence for the pivotal role of PAI-1 during aging and the development of PF.Our research demonstrates that PAI-1,a crucial factor secreted by aging AT2 cells,exerts a pivotal role in promoting the synthesis of Col1a1 in fibroblasts,subsequently leading to Col I deposition,and in driving the progression of PF by mediating the TGF-b/Smad2/3 pathway.Our find-ings offer critical evidence for the involvement of epithelial dysfunction in age-related PF and provides potential novel therapeutic targets for clinical intervention.展开更多
基金supported by the Young Elite Scientist Sponsorship Program by CAST(2022QNRC001)the 111 project of the Education Ministry of China(B18053).
文摘Pulmonary fibrosis(PF)is a lethal lung disease that predominantly affects older adults;however,whether and how aging triggers fibrosis remains unclear.To pinpoint the predominant initiating factors of PF,we first analyzed single-cell RNA sequencing(scRNA-seq)data from the lung tissues of 45 normal donors and 51 PF patients and found that aging might serve as the primary catalyst for PF development.To further investigate the influence of aging on PF formation,we conducted a comprehensive and thorough study employing a natural aging mouse model.We found that dynamic alterations in the quantity and types of collagen fibers during aging-induced PF progression,especially in collagenous(Col)I,emerged as the predominant driver of PF.We then investigated the regulation of Col I synthesis during aging using primary alveolar type 2(AT2)cells and A549 cells line through conditioned media and Transwell cocul-ture,and found that secretions—particularly plasminogen activator inhibitor(PAI)-1—from aged AT2 cells promoted fibrosis and enhanced collagen type I alpha 1(Col1al)production via the transforming growth factor(TGF)-b/small mother against decapentaplegic(Smad)2/3 pathway.Furthermore,scRNA-seq and a histological analysis of human lung tissue demonstrated a significant upregulation of SERPINE1(the gene encoding PAI-1)and PAI-1 expression in both aging lung tissue and AT2 cells,which was consistent with our findings from animal experiments,providing additional evidence for the pivotal role of PAI-1 during aging and the development of PF.Our research demonstrates that PAI-1,a crucial factor secreted by aging AT2 cells,exerts a pivotal role in promoting the synthesis of Col1a1 in fibroblasts,subsequently leading to Col I deposition,and in driving the progression of PF by mediating the TGF-b/Smad2/3 pathway.Our find-ings offer critical evidence for the involvement of epithelial dysfunction in age-related PF and provides potential novel therapeutic targets for clinical intervention.
