title: Emodin-mediated cross-linking enhancement for extracellular matrix homeostasis.
abstract: The extracellular matrix (ECM) is an essential element of mammalian organisms, and its cross-linking formation plays a vital role in ECM development and postnatal homeostasis. Defects in cross-link formation caused by aging, genetic, or environmental factors are known to cause numerous diseases in mammals. To augment the cross-linking formation of ECM, the present study established a ZsGreen reporter system controlled by the promoter of lysyl oxidase-like 1 gene (LOXL1), which serves as both a scaffold element and a cross-linking enzyme in the ECM. By using this system in a drug screen, we identified emodin as a strong enhancer of LOXL1 expression that promoted cross-linking formation of ECM in all the tested systems, including human fibroblast cells, cultured human skin tissues, and animals that received long-term emodin treatment. Collectively, the results suggest that emodin may serve as an effective drug or supplement for ECM homeostasis.
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Jian
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Chen
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Shi
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shuzhang
authors.initials: S
authors.lastname: Yang
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Lu
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Qionglan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Guotong
authors.initials: G
authors.lastname: Xu
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; College of Life Sciences, Shenzhen University, Shenzhen, China. Electronic address: yingming@szu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Ying
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; College of Life Sciences, Shenzhen University, Shenzhen, China. Electronic address: xqliu@tongji.edu.cn.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003895:Desmosine / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D004642:Emodin / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D047428:Protein Kinase Inhibitors; D003895:Desmosine; D004549:Elastin; D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human; D004642:Emodin; D006909:Hydroxyproline
keywords: Cross-linking; Emodin; Extracellular matrix (ECM); Lysyl oxidase-like 1 (LOXL1)