Inhibition of miR122a by Lactobacillus rhamnosus GG culture supernatant increases intestinal occludin expression and protects mice from alcoholic liver disease.
Alcoholic liver disease (ALD) has a high morbidity and mortality. Chronic alcohol consumption causes disruption of intestinal microflora homeostasis, intestinal tight junction barrier dysfunction, increased endotoxemia, and eventually liver steatosis/steatohepatitis. Probiotic Lactobacillus rhamnosus GG (LGG) and the bacteria-free LGG culture supernatant (LGGs) have been shown to promote intestinal epithelial integrity and protect intestinal barrier function in ALD. However, little is known about how LGGs mechanistically works to increase intestinal tight junction proteins. Here we show that chronic ethanol exposure increased intestinal miR122a expression, which decreased occludin expression leading to increased intestinal permeability. Moreover, LGGs supplementation decreased ethanol-elevated miR122a level and attenuated ethanol-induced liver injury in mice. Similar to the effect of ethanol exposure, overexpression of miR122a in Caco-2 monolayers markedly decreased occludin protein levels. In contrast, inhibition of miR122a increased occludin expression. We conclude that LGGs supplementation functions in intestinal integrity by inhibition of miR122a, leading to occludin restoration in mice exposed to chronic ethanol.
School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China; Department of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Haiyang
H
Zhao
Department of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, China.
Cuiqing
C
Zhao
School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China; Department of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Yuanyuan
Y
Dong
Department of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States; Schools of Life Sciences and Technology, and Food Sciences and Technology, Jilin Agricultural University, Changchun, Jilin 130118, China.
Min
M
Zhang
Department of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States; Schools of Life Sciences and Technology, and Food Sciences and Technology, Jilin Agricultural University, Changchun, Jilin 130118, China.
Yuhua
Y
Wang
Department of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States.
Fengyuan
F
Li
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Xiaokun
X
Li
Department of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States; Robley Rex VA Medical Center, Louisville, KY 40202, United States.
Craig
C
McClain
School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China. Electronic address: bioshuliny@yahoo.com.cn.
Shulin
S
Yang
Department of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: wenke.feng@louisville.edu.
Wenke
W
Feng
D000818:Animals; D018938:Caco-2 Cells / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D052201:Lacticaseibacillus rhamnosus / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000502:physiology; D062793:Occludin / Q000096:biosynthesis*; D019936:Probiotics / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction
D035683:MicroRNAs; C544354:Mirn122 microRNA, mouse; D062793:Occludin; C568986:Ocln protein, mouse
Alcohol; Intestine; Lactobacillus rhamnosus GG; Occludin; miR122a