Marinkovic Milos, Tran Olivia N, Wang Hanzhou, Abdul-Azees Parveez, Dean David D, Chen Xiao-Dong, Yeh Chih-Ko
Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA.
Research Service, South Texas Veterans Health Care System, San Antonio, TX, 78229-4404, USA.
J Oral Biol Craniofac Res. 2023 Nov-Dec;13(6):693-703. doi: 10.1016/j.jobcr.2023.08.009. Epub 2023 Sep 12.
Salivary gland (SG) extracellular matrix (ECM) has a major influence on tissue development, homeostasis, and tissue regeneration after injury. During aging, disease, and physical insult, normal remodeling of the SG microenvironment (i.e. ECM) becomes dysregulated, leading to alterations in matrix composition which disrupt tissue architecture/structure, alter cell activity, and negatively impact gland function. Matrix metalloproteinases (MMPs) are a large and diverse family of metalloendopeptidases which play a major role in matrix degradation and are intimately involved in regulating development and cell function; dysregulation of these enzymes leads to the production of a fibrotic matrix. In the SG this altered fibrotic ECM (or cell microenvironment) negatively impacts normal cell function and the effectiveness of gene and stem cell therapies which serve as a foundation for many SG regenerative therapies. For this reason, prospective regenerative strategies should prioritize the maintenance and/or restoration of a healthy SG ECM. Mesenchymal stem cells (MSCs) have great potential for mitigating damage to the SG microenvironment by ameliorating inflammation, reducing fibrosis, and repairing the damaged milieu of extracellular regulatory cues, including the matrix. This review addresses our current understanding of the impact of aging and disease on the SG microenvironment and suggests critical deficiencies and opportunities in ECM-targeted therapeutic interventions.
唾液腺（SG）细胞外基质（ECM）对组织发育、内环境稳态以及损伤后的组织再生具有重大影响。在衰老、疾病和物理损伤过程中，SG微环境（即ECM）的正常重塑会失调，导致基质成分改变，进而破坏组织结构，改变细胞活性，并对腺体功能产生负面影响。基质金属蛋白酶（MMPs）是一个庞大且多样的金属内肽酶家族，在基质降解中起主要作用，并密切参与调节发育和细胞功能；这些酶的失调会导致纤维化基质的产生。在SG中，这种改变的纤维化ECM（或细胞微环境）会对正常细胞功能以及基因和干细胞疗法的有效性产生负面影响，而这些疗法是许多SG再生疗法的基础。因此，前瞻性的再生策略应优先考虑维持和/或恢复健康的SG ECM。间充质干细胞（MSCs）具有通过减轻炎症、减少纤维化以及修复包括基质在内的细胞外调节信号的受损环境来减轻SG微环境损伤的巨大潜力。本综述阐述了我们目前对衰老和疾病对SG微环境影响的理解，并指出了以ECM为靶点的治疗干预措施中的关键不足和机遇。
