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 I gene (L0XL1), 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 erhodin 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. (C) 2014 Elsevier Inc. All rights reserved.