Nerve growth factor upregulates sirtuin 1 expression in cholestasis: a potential therapeutic target

• DOI: 10.1038/emm.2017.235
• Publication Date: 2018-01-12T14:31:04Z
• Authors: Ming-Shian Tsai; Po-Huang Lee; Cheuk-Kwan Sun; Ting-Chia Chiu; Yu-Chun Lin; I-Wei Chang; Po-Han Chen; Ying-Hsien Kao
• Keywords: Hepatolithiasis; Sirtuin 1

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression cholestatic livers. We evaluated NGF and its cognate receptors human livers with hepatolithiasis effects therapy on liver injury hepatic SIRT1 a bile duct ligation (BDL) mouse model. Histopathological molecular analyses showed that hepatocytes diseased expressed NGF, proNGF (a precursor NGF), TrkA p75NTR, whereas only p75NTR was upregulated hepatolithiasis, compared non-hepatolithiasis In BDL model without therapy, but not antagonism, significantly deteriorated BDL-induced injury. By contrast, hepatoprotective effect abrogated by antagonism animals receiving therapy. Intriguingly, positive correlation between found vitro studies demonstrated Huh-7 rodent hepatocytes. Both induced protective against hydrogen peroxide-induced cytotoxicity cells, inhibition activity prevented oxidative cell death. Mechanistically, proNGF, via nuclear (NF)-κB activity, NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase NF-κB signaling were involved These findings suggest pharmacological manipulation NGF/SIRT1 axis might serve as novel approach for treatment disease. A pathway linked to gallstone-induced disease could provide new therapeutic target, say researchers Taiwan. Hepatolithiasis, blockage flow from small intestine gallstones, can lead failure Ming-Shian Tsai co-workers at I-Shou University Kaohsiung widely studied protein is strongly cells patients, decided try using treat mice similar disorders. They increased led levels an anti-aging called 1, death cells. The therefore manipulating NGF/sirtuin treating