Modulation of hepatic stellate cells by Mutaflor® probiotic in non-alcoholic fatty liver disease management
Modulation of hepatic stellate cells by Mutaflor® probiotic in non-alcoholic fatty liver disease management
Background: NAFLD and NASH are emerging as primary causes of chronic liver disease, indicating a need for an effective treatment. Mutaflor® probiotic, a microbial treatment of interest, was effective in sustaining remission in ulcerative colitis patients. Objective: To construct a genetic-epigenetic network linked to HSC signaling as a modulator of NAFLD/NASH pathogenesis, then assess the effects of Mutaflor
® on this network. Methods: First, in silico analysis was used to construct a genetic-epigenetic network linked to HSC signaling. Second, an investigation using rats, including HFHSD induced NASH and Mutaflor
® treated animals, was designed. Experimental procedures included biochemical and histopathologic analysis of rat blood and liver samples. At the molecular level, the expression of genetic (FOXA2, TEAD2, and LATS2 mRNAs) and epigenetic (miR-650, RPARP AS-1 LncRNA) network was measured by real-time PCR. PCR results were validated with immunohistochemistry (α-SMA and LATS2). Target effector proteins, IL-6 and TGF-β, were estimated by ELISA. Results: Mutaflor
® administration minimized biochemical and histopathologic alterations caused by NAFLD/NASH. HSC activation and expression of profibrogenic IL-6 and TGF-β effector proteins were reduced via inhibition of hedgehog and hippo pathways. Pathways may have been inhibited through upregulation of RPARP AS-1 LncRNA which in turn downregulated the expression of miR-650, FOXA2 mRNA and TEAD2 mRNA and upregulated LATS2 mRNA expression. Conclusion: Mutaflor
® may slow the progression of NAFLD/NASH by modulating a genetic-epigenetic network linked to HSC signaling. The probiotic may be a useful modality for the prevention and treatment of NAFLD/NASH.
E. coli, Hedgehog, Hepatic Stellate cells, Hippo, Liver fibrosis, NAFLD, NASH, Probiotic
Hany, Noha M
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Eissa, Sanaa
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Basyouni, Manal
afd7a873-ac10-4f81-ad9f-85964297a707
Hasanin, Amany H
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Aboul-Ela, Yasmin M
97e9f7a0-8e44-46d4-9463-36c7d534f9b1
Elmagd, Nagwa M Abo
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Montasser, Iman F
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Ali, Mahmoud A
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Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Matboli, Marwa
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30 July 2022
Hany, Noha M
32702557-8ffa-4822-8950-791521f6d059
Eissa, Sanaa
dc7552fb-20dd-4617-b065-4b0f41e7fd5e
Basyouni, Manal
afd7a873-ac10-4f81-ad9f-85964297a707
Hasanin, Amany H
4172e1ec-b85a-4852-97f0-5f4458e7daaf
Aboul-Ela, Yasmin M
97e9f7a0-8e44-46d4-9463-36c7d534f9b1
Elmagd, Nagwa M Abo
98938e53-0e47-40d7-b38c-1f928edc910c
Montasser, Iman F
b13ba2c0-0067-4bfe-a60a-e967f7f45ec1
Ali, Mahmoud A
29e16219-808a-4ae0-bfb7-97bfb9dcf21c
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Matboli, Marwa
9d6d5d63-c4b5-4407-b774-c19062c7fdfb
Hany, Noha M, Eissa, Sanaa, Basyouni, Manal, Hasanin, Amany H, Aboul-Ela, Yasmin M, Elmagd, Nagwa M Abo, Montasser, Iman F, Ali, Mahmoud A, Skipp, Paul and Matboli, Marwa
(2022)
Modulation of hepatic stellate cells by Mutaflor® probiotic in non-alcoholic fatty liver disease management.
Journal of Translational Medicine, 20 (1), [342].
(doi:10.1186/s12967-022-03543-z).
Abstract
Background: NAFLD and NASH are emerging as primary causes of chronic liver disease, indicating a need for an effective treatment. Mutaflor® probiotic, a microbial treatment of interest, was effective in sustaining remission in ulcerative colitis patients. Objective: To construct a genetic-epigenetic network linked to HSC signaling as a modulator of NAFLD/NASH pathogenesis, then assess the effects of Mutaflor
® on this network. Methods: First, in silico analysis was used to construct a genetic-epigenetic network linked to HSC signaling. Second, an investigation using rats, including HFHSD induced NASH and Mutaflor
® treated animals, was designed. Experimental procedures included biochemical and histopathologic analysis of rat blood and liver samples. At the molecular level, the expression of genetic (FOXA2, TEAD2, and LATS2 mRNAs) and epigenetic (miR-650, RPARP AS-1 LncRNA) network was measured by real-time PCR. PCR results were validated with immunohistochemistry (α-SMA and LATS2). Target effector proteins, IL-6 and TGF-β, were estimated by ELISA. Results: Mutaflor
® administration minimized biochemical and histopathologic alterations caused by NAFLD/NASH. HSC activation and expression of profibrogenic IL-6 and TGF-β effector proteins were reduced via inhibition of hedgehog and hippo pathways. Pathways may have been inhibited through upregulation of RPARP AS-1 LncRNA which in turn downregulated the expression of miR-650, FOXA2 mRNA and TEAD2 mRNA and upregulated LATS2 mRNA expression. Conclusion: Mutaflor
® may slow the progression of NAFLD/NASH by modulating a genetic-epigenetic network linked to HSC signaling. The probiotic may be a useful modality for the prevention and treatment of NAFLD/NASH.
Text
s12967-022-03543-z
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More information
Accepted/In Press date: 17 July 2022
Published date: 30 July 2022
Additional Information:
Funding Information:
Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). STDF-Science and Technology Development Fund for accredited centers of scientific excellence., Cairo, Egypt (Grant No. 4118 51).
Publisher Copyright:
© 2022, The Author(s).
Keywords:
E. coli, Hedgehog, Hepatic Stellate cells, Hippo, Liver fibrosis, NAFLD, NASH, Probiotic
Identifiers
Local EPrints ID: 472806
URI: http://eprints.soton.ac.uk/id/eprint/472806
ISSN: 1479-5876
PURE UUID: 8ac1b478-7865-4fa7-a3cb-33cc96608054
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Date deposited: 19 Dec 2022 17:44
Last modified: 02 May 2024 01:32
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Contributors
Author:
Noha M Hany
Author:
Sanaa Eissa
Author:
Manal Basyouni
Author:
Amany H Hasanin
Author:
Yasmin M Aboul-Ela
Author:
Nagwa M Abo Elmagd
Author:
Iman F Montasser
Author:
Mahmoud A Ali
Author:
Marwa Matboli
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