Department of Respiratory Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Respiratory Medicine, People's Hospital of Tongnan District, Chongqing, China.
Clin Sci (Lond). 2024 Jul 3;138(13):797-815. doi: 10.1042/CS20240179.
IGFBP7 has been found to play an important role in inflammatory diseases, such as acute lung injury (ALI). However, the role of IGFBP7 in different stages of inflammation remains unclear. Transcriptome sequencing was used to identify the regulatory genes of IGFBP7, and endothelial IGFBP7 expression was knocked down using Aplnr-Dre mice to evaluate the endothelial proliferation capacity. The expression of proliferation-related genes was detected by Western blotting and RT-PCR assays. In the present study, we found that knockdown of IGFBP7 in endothelial cells significantly decreases the expression of endothelial cell proliferation-related genes and cell number in the recovery phase but not in the acute phase of ALI. Mechanistically, using bulk-RNA sequencing and CO-IP, we found that IGFBP7 promotes phosphorylation of FOS and subsequently up-regulates YAP1 molecules, thereby promoting endothelial cell proliferation. This study indicated that IGFBP7 has diverse roles in different stages of ALI, which extends the understanding of IGFBP7 in different stages of ALI and suggests that IGFBP7 as a potential therapeutic target in ALI needs to take into account the period specificity of ALI.
IGFBP7 在炎症性疾病中发挥着重要作用，如急性肺损伤（ALI）。然而，IGFBP7 在炎症不同阶段的作用尚不清楚。本研究采用转录组测序技术鉴定 IGFBP7 的调控基因，并用 Aplnr-Dre 小鼠敲低内皮细胞 IGFBP7 表达，评估内皮细胞的增殖能力。采用 Western blot 和 RT-PCR 检测增殖相关基因的表达。研究发现，内皮细胞中 IGFBP7 的敲低显著降低了 ALI 恢复阶段而非急性阶段内皮细胞增殖相关基因的表达和细胞数量。通过 bulk-RNA 测序和 CO-IP 实验，发现 IGFBP7 促进 FOS 的磷酸化，进而上调 YAP1 分子，从而促进内皮细胞增殖。本研究表明，IGFBP7 在 ALI 的不同阶段发挥着不同的作用，这扩展了对 IGFBP7 在 ALI 不同阶段的认识，并表明 IGFBP7 作为 ALI 的潜在治疗靶点需要考虑 ALI 的时期特异性。
