Enshuang Guo PhD , Huixing Yuan PhD , Renlong Li PhD , Jiankun Yang BS , Shenpei Liu BS , Anding Liu PhD , Xiaojing Jiang PhD
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引用次数: 0
Abstract
Background
Calcitriol has the potential to counteract fibrotic diseases beyond its classical action of maintaining calcium and bone metabolism; however, its functional mechanism remains unknown. Autophagy-related gene 16-like 1 (Atg16l1) is one of the genes related to autophagy and is involved in protecting against fibrotic diseases. The present study aimed to explore the contribution of autophagy to the inhibition of calcitriol-induced hepatic fibrosis, as well as its potential molecular mechanism.
Methods
Carbon tetrachloride (Ccl4)-treated mice were established as hepatic fibrosis models and received calcitriol treatment for 6 weeks. Quantification of Sirius red staining and measurement of key fibrotic markers (collagen-1 and α-SMA) was performed to detect hepatic fibrosis. Chloroquine (CQ) treatment was used to observe autophagic flux, and 3-methyladenine (3-MA) was used to inhibit autophagy. Furthermore, the effects of calcitriol on transforming growth factor β1 (TGFβ1)-stimulated primary hepatic stellate cells (HSCs) were detected. Downregulation of Atg16l1 or vitamin D receptor (VDR) in LX-2 cells was used to explore the mechanism of action of calcitriol in fibrosis and autophagy. Additionally, the electrophoretic mobility shift assay (EMSA) was used to investigate the interactions between VDR and ATG16L1.
Results
Calcitriol increased the expression of VDR and ATG16L1, enhanced autophagy and attenuated hepatic fibrosis. 3-MA treatment and VDR silencing abolished the protective effects of calcitriol against fibrosis. Calcitriol-induced anti-fibrosis effects were blocked by ATG16L1 suppression. Furthermore, VDR bound to the ATG16L1 promoter and downregulation of VDR decreased the expression of ATG16L1 in LX-2 cells.
Conclusion
Calcitriol mitigates hepatic fibrosis partly through ATG16L1-mediated autophagy.
期刊介绍:
The American Journal of The Medical Sciences (AJMS), founded in 1820, is the 2nd oldest medical journal in the United States. The AJMS is the official journal of the Southern Society for Clinical Investigation (SSCI). The SSCI is dedicated to the advancement of medical research and the exchange of knowledge, information and ideas. Its members are committed to mentoring future generations of medical investigators and promoting careers in academic medicine. The AJMS publishes, on a monthly basis, peer-reviewed articles in the field of internal medicine and its subspecialties, which include:
Original clinical and basic science investigations
Review articles
Online Images in the Medical Sciences
Special Features Include:
Patient-Centered Focused Reviews
History of Medicine
The Science of Medical Education.