Effects and mechanisms of melatonin on autophagy and inhibition of hepatic stellate cell proliferation
10.19405/j.cnki.issn1000-1492.2023.11.018
- Author:
Difei Chen
1
;
Lei Jie
1
;
Qiming Huang
1
;
Dexiang Xu
2
;
Xiaofei Ren
1
;
Rutao Hong
1
Author Information
1. Dept of Gastroenterology , The First Afiliated Hospital of Anhui Medical University , Key Laboratory of Disease of Anhui Province , Hefei 230022
2. Dept of Toxicology , Anhui Medical University, Key Laboratory of Anhui Province , Hefei 230032
- Publication Type:Journal Article
- Keywords:
melatonin;
liver cirrhosis;
hepatic stellate cells;
autophagy;
PDGF⁃BB
- From:
Acta Universitatis Medicinalis Anhui
2023;58(11):1910-1915
- CountryChina
- Language:Chinese
-
Abstract:
Objective : To investigate the effects of melatonin ( MEL) on the proliferation of hepatic stellate cells
(HSCs) induced by platelet - derived growth factor (PDGF⁃BB) and explore its correlation with the regulation of autophagy levels .
Methods :The HSC⁃T6 cells were divided into the following groups : control group , model group and MEL (low , medium and high) treatment groups . After 24 hours culture , the cells adhered to the wall and were changed into serum⁃free DMEM medium to synchronize the cells to the G0 stage . After 24 hours culture , all groups were given with PDGF ⁃ BB ( 10 ng/ml) excepted the control group . Besides , melatonin of different concentrations ( 1 nmol/L , 1 μmol/L and 0. 1 mmol/L) were added immediately in three treated groups . After incubated for 48 hours , the effect of MEL on the proliferation of hepatic stellate cells activated by PDGF⁃BB was detected by CCK8 method . The protein expression levels of LC3b and α ⁃SMA in hepatic stellate cells were determined by Western blot . The expression levels of LC3b mRNA and α ⁃SMA mRNA in hepatic stellate cells were determined by qRT⁃PCR . The ultrastructure of HSCs was observed by transmission electron microscopy to understand the autophagy level.
Results : Compared with control group , PDGF⁃BB could induce the proliferation of HSCs ( P < 0. 01) . Compared with model group , MEL inhibited the proliferation of HSCs activated by PDGF⁃BB ( P < 0. 01) . Compared with the control group , LC3b and α ⁃SMA protein expressions significantly increased in the model group ( all P < 0. 05) , and LC3b mRNA and α ⁃SMA mRNA expressions significantly increased in the model group (P < 0. 05 , P < 0. 01) . Compared with the model group , MEL could inhibit such effects (LC3b : P < 0. 05 , P < 0. 01 ; α ⁃SMA : P < 0. 01) . Transmission electron microscopy ( TEM) showed that compared with the control group , autopolysosome significantly increased in the model group (P < 0. 05) . Compared with model group , autopolysosome significantly decreased in MEL treatment group (P < 0. 01) .
Conclusion :The up⁃regulation of autophagy level can promote the proliferation of hepatic stellate cells and the inhibition of hepatic stellate cell proliferation by MEL may be related to the down⁃regulation of autophagy level .
- Full text:2024071117300881594褪黑素调控自噬抑制肝星状细胞增殖的作用及机制研究_陈涤非.pdf
