FGF1 Signaling Modulates Biliary Injury and Liver Fibrosis in the Mdr2−/− Mouse Model of Primary Sclerosing Cholangitis Article Swipe
April O’Brien
,
Tianhao Zhou
,
Tori White
,
Abigail Medford
,
Lixian Chen
,
Konstantina Kyritsi
,
Nan Wu
,
J. R. Childs
,
Danaleigh Stiles
,
Ludovica Ceci
,
Sanjukta Chakraborty
,
Burcin Ekser
,
Leonardo Baiocchi
,
Guido Carpino
,
Eugenio Gaudio
,
Chaodong Wu
,
Lindsey Kennedy
,
Heather Francis
,
Gianfranco Alpini
,
Shannon Glaser
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1002/hep4.1909
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1002/hep4.1909
Fibroblast growth factor 1 (FGF1) belongs to a family of growth factors involved in cellular growth and division. MicroRNA 16 (miR‐16) is a regulator of gene expression, which is dysregulated during liver injury and insult. However, the role of FGF1 in the progression of biliary proliferation, senescence, fibrosis, inflammation, angiogenesis, and its potential interaction with miR‐16, are unknown. In vivo studies were performed in male bile duct–ligated (BDL, 12‐week‐old) mice, multidrug resistance 2 knockout (Mdr2 −/−) mice (10‐week‐old), and their corresponding controls, treated with recombinant human FGF1 (rhFGF1), fibroblast growth factor receptor (FGFR) antagonist (AZD4547), or anti‐FGF1 monoclonal antibody (mAb). In vitro , the human cholangiocyte cell line (H69) and human hepatic stellate cells (HSCs) were used to determine the expression of proliferation, fibrosis, angiogenesis, and inflammatory genes following rhFGF1 treatment. PSC patient and control livers were used to evaluate FGF1 and miR‐16 expression. Intrahepatic bile duct mass (IBDM), along with hepatic fibrosis and inflammation, increased in BDL mice treated with rhFGF1, with a corresponding decrease in miR‐16, while treatment with AZD4547 or anti‐FGF1 mAb decreased hepatic fibrosis, IBDM, and inflammation in BDL and Mdr2 −/− mice. In vitro, H69 and HSCs treated with rhFGF1 had increased expression of proliferation, fibrosis, and inflammatory markers. PSC samples also showed increased FGF1 and FGFRs with corresponding decreases in miR‐16 compared with healthy controls. Conclusion: Our study demonstrates that suppression of FGF1 and miR‐16 signaling decreases the presence of hepatic fibrosis, biliary proliferation, inflammation, senescence, and angiogenesis. Targeting the FGF1 and miR‐16 axis may provide therapeutic options in treating cholangiopathies such as PSC.
Related Topics
Concepts
Fibrosis
Angiogenesis
Hepatic stellate cell
Inflammation
Fibroblast growth factor
Internal medicine
Fibroblast growth factor receptor
Cancer research
Biology
FGF1
Endocrinology
Medicine
Receptor
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/hep4.1909
- OA Status
- gold
- Cited By
- 7
- References
- 52
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4220701194
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4220701194Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1002/hep4.1909Digital Object Identifier
- Title
-
FGF1 Signaling Modulates Biliary Injury and Liver Fibrosis in the Mdr2−/− Mouse Model of Primary Sclerosing CholangitisWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-03-10Full publication date if available
- Authors
-
April O’Brien, Tianhao Zhou, Tori White, Abigail Medford, Lixian Chen, Konstantina Kyritsi, Nan Wu, J. R. Childs, Danaleigh Stiles, Ludovica Ceci, Sanjukta Chakraborty, Burcin Ekser, Leonardo Baiocchi, Guido Carpino, Eugenio Gaudio, Chaodong Wu, Lindsey Kennedy, Heather Francis, Gianfranco Alpini, Shannon GlaserList of authors in order
- Landing page
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https://doi.org/10.1002/hep4.1909Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1002/hep4.1909Direct OA link when available
- Concepts
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Fibrosis, Angiogenesis, Hepatic stellate cell, Inflammation, Fibroblast growth factor, Internal medicine, Fibroblast growth factor receptor, Cancer research, Biology, FGF1, Endocrinology, Medicine, ReceptorTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
7Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 3, 2022: 1Per-year citation counts (last 5 years)
- References (count)
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52Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| publication_date | 2022-03-10 |
| publication_year | 2022 |
| referenced_works | https://openalex.org/W1969051655, https://openalex.org/W2781744819, https://openalex.org/W4211088821, https://openalex.org/W6808758462, https://openalex.org/W3046456815, https://openalex.org/W2899751126, https://openalex.org/W2229729310, https://openalex.org/W2972693655, https://openalex.org/W1965149282, https://openalex.org/W2950947980, https://openalex.org/W1992598298, https://openalex.org/W2469633610, https://openalex.org/W2767242423, https://openalex.org/W2766689053, https://openalex.org/W2256533911, https://openalex.org/W2065303540, https://openalex.org/W2019711215, https://openalex.org/W2153549414, https://openalex.org/W2322804590, https://openalex.org/W2024650311, https://openalex.org/W2973137589, https://openalex.org/W3009944537, https://openalex.org/W2124288445, https://openalex.org/W2761134105, https://openalex.org/W2064227724, https://openalex.org/W2018286119, https://openalex.org/W2562949639, https://openalex.org/W6731339912, https://openalex.org/W2972310443, https://openalex.org/W2745395409, https://openalex.org/W2794969179, https://openalex.org/W2594155820, https://openalex.org/W2044686871, https://openalex.org/W2291693837, https://openalex.org/W2401396814, https://openalex.org/W2621109592, https://openalex.org/W2344909233, https://openalex.org/W2338564836, https://openalex.org/W3001067979, https://openalex.org/W2989673421, https://openalex.org/W2806513401, https://openalex.org/W1539520316, https://openalex.org/W7074224893, https://openalex.org/W2083019610, https://openalex.org/W2141980602, https://openalex.org/W3107290758, https://openalex.org/W3024173350, https://openalex.org/W3044467369, https://openalex.org/W2073504803, https://openalex.org/W2021584389, https://openalex.org/W2117651804, https://openalex.org/W2986691533 |
| referenced_works_count | 52 |
| abstract_inverted_index., | 102 |
| abstract_inverted_index.1 | 3 |
| abstract_inverted_index.2 | 72 |
| abstract_inverted_index.a | 7, 22, 163 |
| abstract_inverted_index.16 | 19 |
| abstract_inverted_index.In | 58, 100, 187 |
| abstract_inverted_index.as | 258 |
| abstract_inverted_index.in | 13, 40, 63, 156, 166, 181, 215, 254 |
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| abstract_inverted_index.or | 95, 172 |
| abstract_inverted_index.to | 6, 117, 138 |
| abstract_inverted_index.BDL | 157, 182 |
| abstract_inverted_index.H69 | 189 |
| abstract_inverted_index.Our | 222 |
| abstract_inverted_index.PSC | 131, 204 |
| abstract_inverted_index.and | 16, 33, 50, 78, 109, 125, 133, 141, 153, 179, 183, 190, 201, 210, 229, 242, 247 |
| abstract_inverted_index.are | 56 |
| abstract_inverted_index.had | 195 |
| abstract_inverted_index.its | 51 |
| abstract_inverted_index.mAb | 174 |
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| abstract_inverted_index.the | 36, 41, 103, 119, 233, 245 |
| abstract_inverted_index.FGF1 | 39, 86, 140, 209, 228, 246 |
| abstract_inverted_index.HSCs | 191 |
| abstract_inverted_index.Mdr2 | 184 |
| abstract_inverted_index.PSC. | 259 |
| abstract_inverted_index.also | 206 |
| abstract_inverted_index.axis | 249 |
| abstract_inverted_index.bile | 65, 145 |
| abstract_inverted_index.cell | 106 |
| abstract_inverted_index.duct | 146 |
| abstract_inverted_index.gene | 25 |
| abstract_inverted_index.line | 107 |
| abstract_inverted_index.male | 64 |
| abstract_inverted_index.mass | 147 |
| abstract_inverted_index.mice | 76, 158 |
| abstract_inverted_index.role | 37 |
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| abstract_inverted_index.that | 225 |
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| abstract_inverted_index.vivo | 59 |
| abstract_inverted_index.were | 61, 115, 136 |
| abstract_inverted_index.with | 54, 83, 150, 160, 162, 170, 193, 212, 218 |
| abstract_inverted_index.(BDL, | 67 |
| abstract_inverted_index.(H69) | 108 |
| abstract_inverted_index.(Mdr2 | 74 |
| abstract_inverted_index.FGFRs | 211 |
| abstract_inverted_index.IBDM, | 178 |
| abstract_inverted_index.along | 149 |
| abstract_inverted_index.cells | 113 |
| abstract_inverted_index.genes | 127 |
| abstract_inverted_index.human | 85, 104, 110 |
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| abstract_inverted_index.mice, | 69 |
| abstract_inverted_index.mice. | 186 |
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| abstract_inverted_index.which | 27 |
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| abstract_inverted_index.(FGF1) | 4 |
| abstract_inverted_index.(FGFR) | 92 |
| abstract_inverted_index.(HSCs) | 114 |
| abstract_inverted_index.(mAb). | 99 |
| abstract_inverted_index.during | 30 |
| abstract_inverted_index.factor | 2, 90 |
| abstract_inverted_index.family | 8 |
| abstract_inverted_index.growth | 1, 10, 15, 89 |
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| abstract_inverted_index.livers | 135 |
| abstract_inverted_index.rhFGF1 | 129, 194 |
| abstract_inverted_index.showed | 207 |
| abstract_inverted_index.vitro, | 188 |
| abstract_inverted_index.(IBDM), | 148 |
| abstract_inverted_index.AZD4547 | 171 |
| abstract_inverted_index.belongs | 5 |
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| abstract_inverted_index.control | 134 |
| abstract_inverted_index.factors | 11 |
| abstract_inverted_index.healthy | 219 |
| abstract_inverted_index.hepatic | 111, 151, 176, 236 |
| abstract_inverted_index.insult. | 34 |
| abstract_inverted_index.options | 253 |
| abstract_inverted_index.patient | 132 |
| abstract_inverted_index.provide | 251 |
| abstract_inverted_index.rhFGF1, | 161 |
| abstract_inverted_index.samples | 205 |
| abstract_inverted_index.studies | 60 |
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| abstract_inverted_index.−/− | 185 |
| abstract_inverted_index.However, | 35 |
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| abstract_inverted_index.cellular | 14 |
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| abstract_inverted_index.evaluate | 139 |
| abstract_inverted_index.fibrosis | 152 |
| abstract_inverted_index.involved | 12 |
| abstract_inverted_index.knockout | 73 |
| abstract_inverted_index.markers. | 203 |
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| abstract_inverted_index.stellate | 112 |
| abstract_inverted_index.treating | 255 |
| abstract_inverted_index.unknown. | 57 |
| abstract_inverted_index.−/−) | 75 |
| abstract_inverted_index.(rhFGF1), | 87 |
| abstract_inverted_index.Targeting | 244 |
| abstract_inverted_index.controls, | 81 |
| abstract_inverted_index.controls. | 220 |
| abstract_inverted_index.decreased | 175 |
| abstract_inverted_index.decreases | 214, 232 |
| abstract_inverted_index.determine | 118 |
| abstract_inverted_index.division. | 17 |
| abstract_inverted_index.fibrosis, | 47, 123, 177, 200, 237 |
| abstract_inverted_index.following | 128 |
| abstract_inverted_index.increased | 155, 196, 208 |
| abstract_inverted_index.miR‐16, | 55, 167 |
| abstract_inverted_index.multidrug | 70 |
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| abstract_inverted_index.potential | 52 |
| abstract_inverted_index.regulator | 23 |
| abstract_inverted_index.signaling | 231 |
| abstract_inverted_index.treatment | 169 |
| abstract_inverted_index.(AZD4547), | 94 |
| abstract_inverted_index.(miR‐16) | 20 |
| abstract_inverted_index.Fibroblast | 0 |
| abstract_inverted_index.antagonist | 93 |
| abstract_inverted_index.expression | 120, 197 |
| abstract_inverted_index.fibroblast | 88 |
| abstract_inverted_index.monoclonal | 97 |
| abstract_inverted_index.resistance | 71 |
| abstract_inverted_index.treatment. | 130 |
| abstract_inverted_index.Conclusion: | 221 |
| abstract_inverted_index.anti‐FGF1 | 96, 173 |
| abstract_inverted_index.expression, | 26 |
| abstract_inverted_index.expression. | 143 |
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| abstract_inverted_index.suppression | 226 |
| abstract_inverted_index.therapeutic | 252 |
| abstract_inverted_index.Intrahepatic | 144 |
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| abstract_inverted_index.inflammation | 180 |
| abstract_inverted_index.inflammatory | 126, 202 |
| abstract_inverted_index.angiogenesis, | 49, 124 |
| abstract_inverted_index.angiogenesis. | 243 |
| abstract_inverted_index.cholangiocyte | 105 |
| abstract_inverted_index.corresponding | 80, 164, 213 |
| abstract_inverted_index.inflammation, | 48, 154, 240 |
| abstract_inverted_index.duct–ligated | 66 |
| abstract_inverted_index.proliferation, | 45, 122, 199, 239 |
| abstract_inverted_index.12‐week‐old) | 68 |
| abstract_inverted_index.cholangiopathies | 256 |
| abstract_inverted_index.(10‐week‐old), | 77 |
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| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5045220703 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 20 |
| corresponding_institution_ids | https://openalex.org/I116067653, https://openalex.org/I4210110049, https://openalex.org/I4394709130, https://openalex.org/I55769427, https://openalex.org/I861853513, https://openalex.org/I91045830 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
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| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.6578885 |
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| citation_normalized_percentile.is_in_top_10_percent | False |