Qi Yifei, Xu Ren
Markey Cancer Center, University of Kentucky, Lexington, KY, United States.
Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, United States.
Front Cell Dev Biol. 2018 Jun 28;6:66. doi: 10.3389/fcell.2018.00066. eCollection 2018.
Collagen is the major component of extracellular matrix. Collagen cross-link and deposition depend on lysyl hydroxylation, which is catalyzed by procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD). Aberrant lysyl hydroxylation and collagen cross-link contributes to the progression of many collagen-related diseases, such as fibrosis and cancer. Three lysyl hydroxylases (LH1, LH2, and LH3) are identified, encoded by , and genes. Expression of PLODs is regulated by multiple cytokines, transcription factors and microRNAs. Dysregulation of PLODs promotes cancer progression and metastasis, suggesting that targeting PLODs is potential strategy for cancer treatment. Here, we summarize the recent progress in the investigation of function and regulation of PLODs in normal tissue development and disease progression, especially in cancer.
胶原蛋白是细胞外基质的主要成分。胶原蛋白的交联和沉积依赖于赖氨酰羟化作用,该作用由原胶原蛋白赖氨酸2-氧戊二酸5-双加氧酶(PLOD)催化。异常的赖氨酰羟化和胶原蛋白交联促进了许多与胶原蛋白相关疾病的进展,如纤维化和癌症。已鉴定出三种赖氨酰羟化酶(LH1、LH2和LH3),分别由、和基因编码。PLOD的表达受多种细胞因子、转录因子和微小RNA的调节。PLOD的失调促进癌症进展和转移,这表明靶向PLOD是一种潜在的癌症治疗策略。在此,我们总结了PLOD在正常组织发育和疾病进展,尤其是癌症中的功能和调控研究的最新进展。