Zhou Xiangjun, Zhang Wei, Yao Qisheng, Zhang Hao, Dong Guie, Zhang Ming, Liu Yutao, Chen Jian-Kang, Dong Zheng
Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei, China.
Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia.
Am J Physiol Renal Physiol. 2017 Jun 1;312(6):F963-F970. doi: 10.1152/ajprenal.00078.2017. Epub 2017 Mar 29.
Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing.
损伤后的肾脏修复涉及到结构和功能完整的肾小管上皮的重建。生长因子及其受体，如表皮生长因子受体（EGFR），在肾小管修复中起着重要作用。外泌体是细胞产生的小囊泡（直径约100纳米），可在细胞间包含并传递蛋白质、脂质、RNA和DNA。在本研究中，我们研究了外泌体产生与EGFR激活之间的关系以及外泌体在伤口愈合中的潜在作用。在肾小管细胞划痕损伤后不久即发生EGFR激活。表皮生长因子（EGF）显著促进划痕损伤后的伤口修复，而EGFR抑制剂吉非替尼则抑制伤口修复。有趣的是，划痕损伤诱导外泌体产生显著增加。EGF使外泌体产生减少，吉非替尼使其增加，提示EGFR信号在外泌体产生中起抑制作用。相反，GW4869和夫西地酸A抑制外泌体释放可显著增加EGFR激活并促进伤口愈合。此外，来自划痕损伤细胞的外泌体可抑制伤口愈合。总体而言，结果表明肾小管细胞的伤口愈合与EGFR激活和外泌体产生有关。虽然EGFR激活促进伤口愈合，但释放的外泌体可能拮抗EGFR激活和伤口愈合。
