Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts.
Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts.
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DOI：
10.1038/s41598-021-86511-9
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发表时间：
2021-03-29
影响因子：
4.6
通讯作者：
Mauney JR
中科院分区：
文献类型：
--
作者：
Gundogdu G;Tosun M;Morhardt D;Gheinani AH;Algarrahi K;Yang X;Costa K;Alegria CG;Adam RM;Yang W;Mauney JR
生物可降解脱细胞移植物对局灶性食管缺损的重建依赖于宿主祖细胞群重新填充植入区域和促进新生功能组织生长的能力。生物材料外科重建后食道修复过程的内在分子机制在很大程度上是未知的。在本研究中，我们利用基于质谱的定量蛋白质组学和硅通路评估来鉴定在Sprague Dawley大鼠脱细胞丝素支架食管成形术模型中新上皮形成过程中显著激活的信号级联。药理学抑制剂和救援实验显示，新组织的上皮化在一定程度上显著依赖于促存活刺激，这种刺激能够通过激活肝细胞生长因子受体（c-MET）、原肌球蛋白受体激酶A （TrkA）、磷酸肌苷3激酶（PI3K）和蛋白激酶B （Akt）信号机制抑制上皮祖细胞中的caspase活性。这些数据强调了脱细胞植入物手术修复后食管上皮再生的分子机制。
Constructive remodeling of focal esophageal defects with biodegradable acellular grafts relies on the ability of host progenitor cell populations to repopulate implant regions and facilitate growth of de novo functional tissue. Intrinsic molecular mechanisms governing esophageal repair processes following biomaterial-based, surgical reconstruction is largely unknown. In the present study, we utilized mass spectrometry-based quantitative proteomics and in silico pathway evaluations to identify signaling cascades which were significantly activated during neoepithelial formation in a Sprague Dawley rat model of onlay esophagoplasty with acellular silk fibroin scaffolds. Pharmacologic inhibitor and rescue experiments revealed that epithelialization of neotissues is significantly dependent in part on pro-survival stimuli capable of suppressing caspase activity in epithelial progenitors via activation of hepatocyte growth factor receptor (c-MET), tropomyosin receptor kinase A (TrkA), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling mechanisms. These data highlight the molecular machinery involved in esophageal epithelial regeneration following surgical repair with acellular implants.
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DOI：
10.1001/archotol.124.10.1146
发表时间：
1998-10-01
影响因子：
--
作者：
Li, KK;Salibian, AH;Kelly, T
通讯作者：
Kelly, T
影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
4.1
作者：
Gundogdu，Gokhan;Morhardt，Duncan;Mauney，Joshua R.
通讯作者：
Mauney，Joshua R.
影响因子：
2.6
作者：
Lopes, M. F.;Cabrita, A.;Patricio, J.
通讯作者：
Patricio, J.
影响因子：
2.4
作者：
Badylak, S;Meurling, S;Simmons-Byrd, A
通讯作者：
Simmons-Byrd, A