CoChat
Sign Up
Cited by 14Liver Disease Diagnosis and TreatmentMicroRNA in disease regulationLiver physiology and pathology

Inhibition of microRNA-33b in humanized mice ameliorates nonalcoholic steatohepatitis

Open access
Miyagawa, Sawa, Horie, Takahiro, Nishino, Tomohiro, Koyama, Satoshi, Watanabe, Toshimitsu, Baba, Osamu, Yamasaki, Tomohiro, Sowa, Naoya +15 more·2023·Life Science Alliance
DOI 10.26508/lsa.202301902PMC PMC10235800
Open this paper in CoChat — free accountOpen PDF

Abstract

Nonalcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma in their advanced stages; however, there are currently no approved therapies. Here, we show that microRNA (miR)-33b in hepatocytes is critical for the development of NASH. miR-33b is located in the intron of sterol regulatory element–binding transcription factor 1 and is abundantly expressed in humans, but absent in rodents. miR-33b knock-in (KI) mice, which have a miR-33b sequence in the same intron of sterol regulatory element–binding transcription factor 1 as humans and express miR-33b similar to humans, exhibit NASH under high-fat diet feeding. This condition is ameliorated by hepatocyte-specific miR-33b deficiency but unaffected by macrophage-specific miR-33b deficiency. Anti-miR-33b oligonucleotide improves the phenotype of NASH in miR-33b KI mice fed a Gubra Amylin NASH diet, which induces miR-33b and worsens NASH more than a high-fat diet. Anti-miR-33b treatment reduces hepatic free cholesterol and triglyceride accumulation through up-regulation of the lipid metabolism–related target genes. Furthermore, it decreases the expression of fibrosis marker genes in cultured hepatic stellate cells. Thus, inhibition of miR-33b using nucleic acid medicine is a promising treatment for NASH.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.26508/lsa.202301902

Cites

12 of 12 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • miR-33b promotes steatohepatitis through its effects on hepatocytes or hepatic stellate cells, and its inhibition by synthetic nucleic acids suppresses steatohepatitis formation by reducing cholesterol and fatty acid accumulation.

    “Furthermore, studies using miR-33b knock-in mice have reported that miR-33b promotes steatohepatitis through its effects on hepatocytes or hepatic stellate cells and that its inhibition by synthetic nucleic acids suppresses steatohepatitis formation by reducing cholesterol and fatty acid accumulation 38) .”

    From Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives (2026) · cites this paper as [38]

    The Discussion (page unavailable) reports that miR-33b in hepatocytes worsened NAFLD/NASH in knock-in mice and that hepatic stellate-cell miR-33b may also contribute. It also reports that anti-miR-33b oligonucleotides reduced liver free cholesterol and triglycerides and improved fibrosis. The paper does not establish that treatment reduced fatty acid accumulation specifically; that part substitutes fatty acids for the measured triglycerides. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 54

  1. Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, (2014) An atlas of active enhancers across human cell types and tissues. Nature 507: 455– 461. 10.1038/nature12787 24670763 PMC5215096 · DOI · Paper page
  2. Auguet T, Aragones G, Berlanga A, Guiu-Jurado E, Marti A, Martinez S, Sabench F, Hernandez M, Aguilar C, Sirvent JJ, (2016) miR33a/miR33b* and miR122 as possible contributors to hepatic lipid metabolism in obese women with nonalcoholic fatty liver disease. Int J Mol Sci 17: 1620. 10.3390/ijms17101620 27669236 PMC5085653 · DOI
  3. Beaven SW, Wroblewski K, Wang J, Hong C, Bensinger S, Tsukamoto H, Tontonoz P (2011) Liver X receptor signaling is a determinant of stellate cell activation and susceptibility to fibrotic liver disease. Gastroenterology 140: 1052– 1062. 10.1053/j.gastro.2010.11.053 21134374 PMC3049833 · DOI · Paper page
  4. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR (1999) Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions. Am J Gastroenterol 94: 2467– 2474. 10.1111/j.1572-0241.1999.01377.x 10484010 · DOI · Paper page
  5. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, (2002) Expanding the natural history of nonalcoholic steatohepatitis: From cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 123: 134– 140. 10.1053/gast.2002.34168 12105842 · DOI
  6. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ, American Gastroenterological Association, American Association for the Study of Liver Diseases, et al (2012). The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American gastroenterological association, American association for the study of liver diseases, and American college of gastroenterology. Gastroenterology 142: 1592– 1609. 10.1053/j.gastro.2012.04.001 22656328 · DOI
  7. Chen G, Liang G, Ou J, Goldstein JL, Brown MS (2004) Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci U S A 101: 11245– 11250. 10.1073/pnas.0404297101 15266058 PMC509189 · DOI
  8. Copeland NG, Jenkins NA, Court DL (2001) Recombineering: A powerful new tool for mouse functional genomics. Nat Rev Genet 2: 769– 779. 10.1038/35093556 11584293 · DOI
  9. Dorn C, Riener MO, Kirovski G, Saugspier M, Steib K, Weiss TS, Gabele E, Kristiansen G, Hartmann A, Hellerbrand C (2010) Expression of fatty acid synthase in nonalcoholic fatty liver disease. Int J Clin Exp Pathol 3: 505– 514. 20606731 PMC2897101
  10. Erhartova D, Cahova M, Dankova H, Heczkova M, Mikova I, Sticova E, Spicak J, Seda O, Trunecka P (2019) Serum miR-33a is associated with steatosis and inflammation in patients with non-alcoholic fatty liver disease after liver transplantation. PLoS One 14: e0224820. 10.1371/journal.pone.0224820 31703079 PMC6839850 · DOI
  11. Ferre P, Foufelle F (2010) Hepatic steatosis: A role for de novo lipogenesis and the transcription factor SREBP-1c. Diabetes Obes Metab 12: 83– 92. 10.1111/j.1463-1326.2010.01275.x 21029304 · DOI
  12. Folch J, Lees M, Stanley GS (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226: 497– 509. 10.1016/s0021-9258(18)64849-5 13428781 · DOI · Paper page
  13. Gan LT, Van Rooyen DM, Koina ME, McCuskey RS, Teoh NC, Farrell GC (2014) Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent. J Hepatol 61: 1376– 1384. 10.1016/j.jhep.2014.07.024 25064435 · DOI
  14. Haldar D, Kern B, Hodson J, Armstrong MJ, Adam R, Berlakovich G, Fritz J, Feurstein B, Popp W, Karam V, (2019) Outcomes of liver transplantation for non-alcoholic steatohepatitis: A European liver transplant registry study. J Hepatol 71: 313– 322. 10.1016/j.jhep.2019.04.011 31071367 PMC6656693 · DOI · Paper page
  15. He J, Zhang G, Pang Q, Yu C, Xiong J, Zhu J, Chen F (2017) SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition. FEBS J 284: 1324– 1337. 10.1111/febs.14055 28296196 · DOI
  16. Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T, Nagao K, Kinoshita M, Kuwabara Y, Marusawa H, Iwanaga Y, (2010a) MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo. Proc Natl Acad Sci U S A 107: 17321– 17326. 10.1073/pnas.1008499107 20855588 PMC2951399 · DOI · Paper page
  17. Horie T, Ono K, Nishi H, Nagao K, Kinoshita M, Watanabe S, Kuwabara Y, Nakashima Y, Takanabe-Mori R, Nishi E, (2010b) Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway. Cardiovasc Res 87: 656– 664. 10.1093/cvr/cvq148 20495188 PMC2920811 · DOI
  18. Horie T, Baba O, Kuwabara Y, Chujo Y, Watanabe S, Kinoshita M, Horiguchi M, Nakamura T, Chonabayashi K, Hishizawa M, (2012) MicroRNA-33 deficiency reduces the progression of atherosclerotic plaque in ApoE(−/−) mice. J Am Heart Assoc 1: e003376. 10.1161/jaha.112.003376 23316322 PMC3540673 · DOI · Paper page
  19. Ioannou GN (2016) The role of cholesterol in the pathogenesis of NASH. Trends Endocrinol Metab 27: 84– 95. 10.1016/j.tem.2015.11.008 26703097 · DOI · Paper page
  20. Kato T, Shimano H, Yamamoto T, Ishikawa M, Kumadaki S, Matsuzaka T, Nakagawa Y, Yahagi N, Nakakuki M, Hasty AH, (2008) Palmitate impairs and eicosapentaenoate restores insulin secretion through regulation of SREBP-1c in pancreatic islets. Diabetes 57: 2382– 2392. 10.2337/db06-1806 18458149 PMC2518489 · DOI
  21. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41: 1313– 1321. 10.1002/hep.20701 15915461 · DOI · Paper page
  22. Koyama S, Horie T, Nishino T, Baba O, Sowa N, Miyasaka Y, Kuwabara Y, Nakao T, Nishiga M, Nishi H, (2019) Identification of differential roles of MicroRNA-33a and -33b during atherosclerosis progression with genetically modified mice. J Am Heart Assoc 8: e012609. 10.1161/jaha.119.012609 31242815 PMC6662357 · DOI · Paper page
  23. Lebeaupin C, Vallee D, Hazari Y, Hetz C, Chevet E, Bailly-Maitre B (2018) Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. J Hepatol 69: 927– 947. 10.1016/j.jhep.2018.06.008 29940269 · DOI
  24. Liang G, Yang J, Horton JD, Hammer RE, Goldstein JL, Brown MS (2002) Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. J Biol Chem 277: 9520– 9528. 10.1074/jbc.m111421200 11782483 · DOI · Paper page
  25. Ludwig J, Viggiano TR, McGill DB, Oh BJ (1980) Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 55: 434– 438. 7382552
  26. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ (1999) Nonalcoholic fatty liver disease: A spectrum of clinical and pathological severity. Gastroenterology 116: 1413– 1419. 10.1016/s0016-5085(99)70506-8 10348825 · DOI · Paper page
  27. Min HK, Kapoor A, Fuchs M, Mirshahi F, Zhou H, Maher J, Kellum J, Warnick R, Contos MJ, Sanyal AJ (2012) Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease. Cell Metab 15: 665– 674. 10.1016/j.cmet.2012.04.004 22560219 PMC3361911 · DOI
  28. Morita M, Ohneda O, Yamashita T, Takahashi S, Suzuki N, Nakajima O, Kawauchi S, Ema M, Shibahara S, Udono T, (2003) HLF/HIF-2α is a key factor in retinopathy of prematurity in association with erythropoietin. EMBO J 22: 1134– 1146. 10.1093/emboj/cdg117 12606578 PMC150350 · DOI
  29. Murakami K, Abe T, Miyazawa M, Yamaguchi M, Masuda T, Matsuura T, Nagamori S, Takeuchi K, Abe K, Kyogoku M (1995) Establishment of a new human cell line, LI90, exhibiting characteristics of hepatic Ito (fat-storing) cells. Lab Invest 72: 731– 739. 7540235
  30. Nishiga M, Horie T, Kuwabara Y, Nagao K, Baba O, Nakao T, Nishino T, Hakuno D, Nakashima Y, Nishi H, (2017) MicroRNA-33 controls adaptive fibrotic response in the remodeling heart by preserving lipid raft cholesterol. Circ Res 120: 835– 847. 10.1161/circresaha.116.309528 27920122 · DOI
  31. Nishino T, Horie T, Baba O, Sowa N, Hanada R, Kuwabara Y, Nakao T, Nishiga M, Nishi H, Nakashima Y, (2018) SREBF1/MicroRNA-33b Axis exhibits potent effect on unstable atherosclerotic plaque formation in vivo. Arterioscler Thromb Vasc Biol 38: 2460– 2473. 10.1161/atvbaha.118.311409 30354203 · DOI · Paper page
  32. Pettinelli P, Videla LA (2011) Up-regulation of PPAR-gamma mRNA expression in the liver of obese patients: An additional reinforcing lipogenic mechanism to SREBP-1c induction. Mol Endocrinol 25: 547– 1430. 10.1210/mend.25.3.zmg547 21325464 · DOI
  33. Powell EE, Wong VW, Rinella M (2021) Non-alcoholic fatty liver disease. The Lancet 397: 2212– 2224. 10.1016/s0140-6736(20)32511-3 33894145 · DOI · Paper page
  34. Price NL, Zhang X, Fernandez-Tussy P, Singh AK, Burnap SA, Rotllan N, Goedeke L, Sun J, Canfran-Duque A, Aryal B, (2021) Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis. Proc Natl Acad Sci U S A 118: e2006478118. 10.1073/pnas.2006478118 33495342 PMC7865172 · DOI · Paper page
  35. Rayner KJ, Suarez Y, Davalos A, Parathath S, Fitzgerald ML, Tamehiro N, Fisher EA, Moore KJ, Fernandez-Hernando C (2010) MiR-33 contributes to the regulation of cholesterol homeostasis. Science 328: 1570– 1573. 10.1126/science.1189862 20466885 PMC3114628 · DOI · Paper page
  36. Rayner KJ, Esau CC, Hussain FN, McDaniel AL, Marshall SM, van Gils JM, Ray TD, Sheedy FJ, Goedeke L, Liu X, (2011a) Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature 478: 404– 407. 10.1038/nature10486 22012398 PMC3235584 · DOI · Paper page
  37. Rong S, Cortes VA, Rashid S, Anderson NN, McDonald JG, Liang G, Moon YA, Hammer RE, Horton JD (2017) Expression of SREBP-1c requires SREBP-2-mediated generation of a sterol ligand for LXR in livers of mice. Elife 6: e25015. 10.7554/elife.25015 28244871 PMC5348127 · DOI · Paper page
  38. Rotllan N, Ramirez CM, Aryal B, Esau CC, Fernandez-Hernando C (2013) Therapeutic silencing of microRNA-33 inhibits the progression of atherosclerosis in Ldlr-/- mice--brief report. Arterioscler Thromb Vasc Biol 33: 1973– 1977. 10.1161/atvbaha.113.301732 23702658 PMC4157595 · DOI · Paper page
  39. Song Y, Liu J, Zhao K, Gao L, Zhao J (2021) Cholesterol-induced toxicity: An integrated view of the role of cholesterol in multiple diseases. Cell Metab 33: 1911– 1925. 10.1016/j.cmet.2021.09.001 34562355 · DOI
  40. Tang CY, Man XF, Guo Y, Tang HN, Tang J, Zhou CL, Tan SW, Wang M, Zhou HD (2017) IRS-2 partially compensates for the insulin signal defects in IRS-1(–/–) mice mediated by miR-33. Mol Cell 40: 123– 132. 10.14348/molcells.2017.2228 PMC5339503 28190325 · DOI
  41. Thaler H (1962) [The fatty liver and its pathogenetic relation to liver cirrhosis]. Virchows Archiv Pathol Anat Physiol Klin Med 335: 180– 210. 10.1007/bf02438705 13920484 · DOI
  42. Van Rooyen DM, Larter CZ, Haigh WG, Yeh MM, Ioannou G, Kuver R, Lee SP, Teoh NC, Farrell GC (2011) Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis. Gastroenterology 141: 1393– 403, 1403.e1-5. 10.1053/j.gastro.2011.06.040 21703998 PMC3186822 · DOI
  43. Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, Landt CL, Harrison SA (2011) Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: A prospective study. Gastroenterology 140: 124– 131. 10.1053/j.gastro.2010.09.038 20858492 · DOI
  44. Wouters K, van Bilsen M, van Gorp PJ, Bieghs V, Lutjohann D, Kerksiek A, Staels B, Hofker MH, Shiri-Sverdlov R (2010) Intrahepatic cholesterol influences progression, inhibition and reversal of non-alcoholic steatohepatitis in hyperlipidemic mice. FEBS Lett 584: 1001– 1005. 10.1016/j.febslet.2010.01.046 20114046 · DOI · Paper page
  45. Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD, Canbay A, Hoffman HM, Feldstein AE (2014) NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology 59: 898– 910. 10.1002/hep.26592 23813842 PMC4008151 · DOI · Paper page
  46. Xie X, Liao H, Dang H, Pang W, Guan Y, Wang X, Shyy JY, Zhu Y, Sladek FM (2009) Down-regulation of hepatic HNF4α gene expression during hyperinsulinemia via SREBPs. Mol Endocrinol 23: 434– 443. 10.1210/me.2007-0531 19179483 PMC2667705 · DOI
  47. Yamaguchi K, Yang L, McCall S, Huang J, Yu XX, Pandey SK, Bhanot S, Monia BP, Li YX, Diehl AM (2007) Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 45: 1366– 1374. 10.1002/hep.21655 17476695 · DOI
  48. Yamamoto T, Yahara A, Waki R, Yasuhara H, Wada F, Harada-Shiba M, Obika S (2015) Amido-bridged nucleic acids with small hydrophobic residues enhance hepatic tropism of antisense oligonucleotides in vivo. Org Biomol Chem 13: 3757– 3765. 10.1039/c5ob00242g 25690587 · DOI
  49. Yamasaki T, Horie T, Koyama S, Nakao T, Baba O, Kimura M, Sowa N, Sakamoto K, Yamazaki K, Obika S, (2022) Inhibition of microRNA-33b specifically ameliorates abdominal aortic aneurysm formation via suppression of inflammatory pathways. Sci Rep 12: 11984. 10.1038/s41598-022-16017-5 35835906 PMC9283493 · DOI · Paper page
  50. Yang H, Arif M, Yuan M, Li X, Shong K, Turkez H, Nielsen J, Uhlen M, Boren J, Zhang C, (2021) A network-based approach reveals the dysregulated transcriptional regulation in non-alcoholic fatty liver disease. iScience 24: 103222. 10.1016/j.isci.2021.103222 34712920 PMC8529555 · DOI
  51. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M (2016) Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64: 73– 84. 10.1002/hep.28431 26707365 · DOI · Paper page
  52. Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J, Bugianesi E (2018) Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 15: 11– 20. 10.1038/nrgastro.2017.109 28930295 · DOI · Paper page
  53. Zhang X, Rotllan N, Canfran-Duque A, Sun J, Toczek J, Moshnikova A, Malik S, Price NL, Araldi E, Zhong W, (2022) Targeted suppression of miRNA-33 using pHLIP improves atherosclerosis regression. Circ Res 131: 77– 90. 10.1161/circresaha.121.320296 35534923 PMC9640270 · DOI · Paper page
  54. Zhao L, Chen Y, Tang R, Chen Y, Li Q, Gong J, Huang A, Varghese Z, Moorhead JF, Ruan XZ (2011) Inflammatory stress exacerbates hepatic cholesterol accumulation via increasing cholesterol uptake and de novo synthesis. J Gastroenterol Hepatol 26: 875– 883. 10.1111/j.1440-1746.2010.06560.x 21488946 · DOI

Cited by

Sorted by citations

Authors
Miyagawa, S., Horie, T., Nishino, T., Koyama, S., Watanabe, T., Baba, O., Yamasaki, T., Sowa, N., Otani, C., Matsushita, K., Kojima, H., Kimura, M., Nakashima, Y., Obika, S., Kasahara, Y., Kotera, J., Oka, K., Fujita, R., Sasaki, T., Takemiya, A., Hasegawa, K., Kimura, T., & Ono, K.
Affiliations
  • Kyoto University (JP)
  • Kyoto Medical Center (JP)
  • National Institute of Biomedical Innovation, Health and Nutrition (JP)
  • Tanabe Pharma Corporation (Japan) (JP)
Corresponding author
  • Horie, Takahiro
  • Ono, Koh
ORCID
Venue
Life Science Alliance
Publisher
Life Science Alliance, LLC
Published
2023-06-01
Volume
6
Issue
8
Pages
e202301902
ISSN
2575-1077 (ISSN-L)
DOI
10.26508/lsa.202301902
PMC
PMC10235800
OpenAlex
W4379094389
Cited by
14
References
12
Citations by year
2025: 6 · 2024: 5 · 2023: 3
FWCI
2.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Life Science Alliance (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
Funders
  • MEXT | Japan Society for the Promotion of Science (17K09860, 20K08904, 17H04177, 17H05599, 20H03675)
  • Japan Agency for Medical Research and Development (21ym0126013h0001)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
nonalcoholic steatohepatitis, humanized mice, hepatocyte-specific knockout, anti-miR oligonucleotides, hepatic lipid metabolism, free cholesterol accumulation, triglyceride accumulation, liver fibrosis, hepatic stellate cells, high-fat diet
MeSH terms
Antagomirs, Animals, Cholesterol, Humans, Liver Neoplasms, Transcription Factors, MicroRNAs, Mice, Non-alcoholic Fatty Liver Disease

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review