Abstract：
The extracellular matrix (ECM) determines functional properties of connective tissues through structural components, such as collagens, elastic fibers, or proteoglycans. The ECM also instructs cell behavior through regulatory proteins, including proteases, growth factors, and matricellular proteins, which can be soluble or tethered to ECM scaffolds. The secreted a disintegrin and metalloproteinase with thrombospondin type 1 repeats/motifs-like (ADAMTSL) proteins constitute a family of regulatory ECM proteins that are related to ADAMTS proteases but lack their protease domains. In mammals, the ADAMTSL protein family comprises seven members, ADAMTSL1-6 and papilin. ADAMTSL orthologs are also present in the worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster. Like other matricellular proteins, ADAMTSL expression is characterized by tight spatiotemporal regulation during embryonic development and early postnatal growth and by cell type- and tissue-specific functional pleiotropy. Although largely quiescent during adult tissue homeostasis, reexpression of ADAMTSL proteins is frequently observed in the context of physiological and pathological tissue remodeling and during regeneration and repair after injury. The diverse functions of ADAMTSL proteins are further evident from disorders caused by mutations in individual ADAMTSL proteins, which can affect multiple organ systems. In addition, genome-wide association studies (GWAS) have linked single nucleotide polymorphisms (SNPs) in ADAMTSL genes to complex traits, such as lung function, asthma, height, body mass, fibrosis, or schizophrenia. In this review, we summarize the current knowledge about individual members of the ADAMTSL protein family and highlight recent mechanistic studies that began to elucidate their diverse functions.
摘要：
细胞外基质（ECM）通过结构成分决定结缔组织的功能特性，如胶原蛋白，弹性纤维,或者蛋白聚糖.ECM还通过调节蛋白指导细胞行为，包括蛋白酶,生长因子，和体细胞蛋白质，其可以是可溶的或束缚于ECM支架。分泌的具有血小板反应蛋白1型重复/基序样（ADAMTSL）蛋白的整合素和金属蛋白酶构成与ADAMTS蛋白酶相关的调节性ECM蛋白家族，但缺乏它们的蛋白酶结构域。在哺乳动物中,ADAMTSL蛋白家族由七个成员组成，ADAMTSL1-6和papilin。ADAMTSL直系同源物也存在于蠕虫中，秀丽隐杆线虫,果蝇，黑腹果蝇.像其他体细胞蛋白一样，ADAMTSL表达的特征是在胚胎发育和出生后早期生长过程中严格的时空调节以及细胞类型和组织特异性功能多效性。虽然在成人组织稳态期间大部分是静止的，在生理和病理组织重塑的背景下以及在损伤后的再生和修复期间经常观察到ADAMTSL蛋白的再表达。ADAMTSL蛋白的不同功能从由单个ADAMTSL蛋白突变引起的疾病中进一步明显。会影响多个器官系统。此外,全基因组关联研究（GWAS）已将ADAMTSL基因中的单核苷酸多态性（SNP）与复杂性状，比如肺功能，哮喘,高度,体重,纤维化，或精神分裂症。在这次审查中,我们总结了当前有关ADAMTSL蛋白家族个体成员的知识,并重点介绍了最近开始阐明其不同功能的机制研究.
