Molecular, Cellular, Developmental, and Neural Biology Graduate Program, State University of New York, University at Albany, Albany, NY, USA.
Department of Biological Sciences, State University of New York, University at Albany, Albany, NY, USA.
J Dent Res. 2020 Jan;99(1):79-88. doi: 10.1177/0022034519889026. Epub 2019 Nov 25.
Regenerative medicine aims to repair, replace, or restore function to tissues damaged by aging, disease, or injury. Partial organ resection is not only a common clinical approach in cancer therapy but also an experimental injury model used to examine mechanisms of regeneration and repair in organs. We performed a partial resection, or partial sialoadenectomy, in the female murine submandibular salivary gland (SMG) to establish a model for investigation of repair mechanisms in salivary glands (SGs). After partial sialoadenectomy, we performed whole-gland measurements over a period of 56 d and found that the gland increased slightly in size. We used microarray analysis and immunohistochemistry (IHC) to examine messenger RNA and protein changes in glands over time. Microarray analysis identified dynamic changes in the transcriptome 3 d after injury that were largely resolved by day 14. At the 3-d time point, we detected gene signatures for cell cycle regulation, inflammatory/repair response, and extracellular matrix (ECM) remodeling in the partially resected glands. Using quantitative IHC, we identified a transient proliferative response throughout the gland. Both secretory epithelial and stromal cells expressed Ki67 that was detectable at day 3 and largely resolved by day 14. IHC also revealed that while most of the gland underwent a wound-healing response that resolved by day 14, a small region of the gland showed an aberrant sustained fibrotic response characterized by increased levels of ECM deposition, sustained Ki67 levels in stromal cells, and a persistent M2 macrophage response through day 56. The partial submandibular salivary gland resection model provides an opportunity to examine a normal healing response and an aberrant fibrotic response within the same gland to uncover mechanisms that prevent wound healing and regeneration in mammals. Understanding regional differences in the wound-healing responses may ultimately affect regenerative therapies for patients.
再生医学旨在修复、替代或恢复因衰老、疾病或损伤而受损的组织。部分器官切除术不仅是癌症治疗中的一种常见临床方法，也是一种用于研究器官再生和修复机制的实验性损伤模型。我们对雌性小鼠下颌下唾液腺（SMG）进行了部分切除术，即部分涎腺切除术，以建立用于研究唾液腺（SG）修复机制的模型。部分涎腺切除术后，我们在 56 天的时间内对整个腺体进行了测量，发现腺体略有增大。我们使用微阵列分析和免疫组织化学（IHC）来随时间检查腺体中的信使 RNA 和蛋白质变化。微阵列分析鉴定了损伤后 3 天的转录组的动态变化，这些变化在第 14 天基本得到解决。在第 3 天时间点，我们在部分切除的腺体中检测到细胞周期调节、炎症/修复反应和细胞外基质（ECM）重塑的基因特征。通过定量 IHC，我们在整个腺体中发现了短暂的增殖反应。分泌上皮细胞和基质细胞均表达 Ki67，可在第 3 天检测到，第 14 天基本消失。IHC 还表明，尽管大部分腺体经历了伤口愈合反应，第 14 天就已解决，但腺体的一小部分表现出异常的持续纤维化反应，其特征是 ECM 沉积水平增加、基质细胞中的 Ki67 水平持续升高，以及第 56 天仍存在 M2 巨噬细胞反应。部分下颌下唾液腺切除术模型提供了一个机会，可在同一腺体中检查正常愈合反应和异常纤维化反应，以揭示阻止哺乳动物伤口愈合和再生的机制。了解伤口愈合反应的区域差异可能最终会影响患者的再生治疗。
