Collagen Characterization in a Model of Nonalcoholic Steatohepatitis with Fibrosis; A Call for Development of Targeted Therapeutics
Left untreated, nonalcoholic fatty liver disease can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and end-stage liver disease. To date, few if any therapies have proven effective against NASH with fibrosis. Quantification and qualification of hepatic scar might enable development of mo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/11/3316 |
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| author | Anthony J. Pellicano Kiera Spahn Ping Zhou Itzhak D. Goldberg Prakash Narayan |
| author_facet | Anthony J. Pellicano Kiera Spahn Ping Zhou Itzhak D. Goldberg Prakash Narayan |
| author_sort | Anthony J. Pellicano |
| collection | DOAJ |
| description | Left untreated, nonalcoholic fatty liver disease can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and end-stage liver disease. To date, few if any therapies have proven effective against NASH with fibrosis. Quantification and qualification of hepatic scar might enable development of more effective targeted therapies. In a murine model of NASH induced by diet, we characterized fibrillar collagen deposition within the hepatic parenchyma. At harvest, livers from the modified diet cohort exhibited NASH with fibrosis. Transcriptomic analysis of hepatic tissue revealed increased <i>col1a1, col1a2,</i> and <i>col3a1,</i> each of which correlated directly with hepatic hydroxyproline content. Circular polarized microscopic analysis of Picrosirius red-stained liver sections revealed deposition of collagen type I within the parenchyma. Development of therapeutics designed to mitigate collagen type I accumulation might prove effective in NASH with fibrosis. |
| first_indexed | 2024-03-10T10:49:20Z |
| format | Article |
| id | doaj.art-faf10a9f32ad420aa4dca518e53ee7d8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:49:20Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-faf10a9f32ad420aa4dca518e53ee7d82023-11-21T22:21:51ZengMDPI AGMolecules1420-30492021-06-012611331610.3390/molecules26113316Collagen Characterization in a Model of Nonalcoholic Steatohepatitis with Fibrosis; A Call for Development of Targeted TherapeuticsAnthony J. Pellicano0Kiera Spahn1Ping Zhou2Itzhak D. Goldberg3Prakash Narayan4Department of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USADepartment of Preclinical Research, Angion Biomedica Corp., 51 Charles Lindbergh Boulevard, Uniondale, NY 11553, USALeft untreated, nonalcoholic fatty liver disease can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and end-stage liver disease. To date, few if any therapies have proven effective against NASH with fibrosis. Quantification and qualification of hepatic scar might enable development of more effective targeted therapies. In a murine model of NASH induced by diet, we characterized fibrillar collagen deposition within the hepatic parenchyma. At harvest, livers from the modified diet cohort exhibited NASH with fibrosis. Transcriptomic analysis of hepatic tissue revealed increased <i>col1a1, col1a2,</i> and <i>col3a1,</i> each of which correlated directly with hepatic hydroxyproline content. Circular polarized microscopic analysis of Picrosirius red-stained liver sections revealed deposition of collagen type I within the parenchyma. Development of therapeutics designed to mitigate collagen type I accumulation might prove effective in NASH with fibrosis.https://www.mdpi.com/1420-3049/26/11/3316precision therapeuticsNASHfibrosiscollagen type Icollagen type IIItranscriptomic |
| spellingShingle | Anthony J. Pellicano Kiera Spahn Ping Zhou Itzhak D. Goldberg Prakash Narayan Collagen Characterization in a Model of Nonalcoholic Steatohepatitis with Fibrosis; A Call for Development of Targeted Therapeutics Molecules precision therapeutics NASH fibrosis collagen type I collagen type III transcriptomic |
| title | Collagen Characterization in a Model of Nonalcoholic Steatohepatitis with Fibrosis; A Call for Development of Targeted Therapeutics |
| title_full | Collagen Characterization in a Model of Nonalcoholic Steatohepatitis with Fibrosis; A Call for Development of Targeted Therapeutics |
| title_fullStr | Collagen Characterization in a Model of Nonalcoholic Steatohepatitis with Fibrosis; A Call for Development of Targeted Therapeutics |
| title_full_unstemmed | Collagen Characterization in a Model of Nonalcoholic Steatohepatitis with Fibrosis; A Call for Development of Targeted Therapeutics |
| title_short | Collagen Characterization in a Model of Nonalcoholic Steatohepatitis with Fibrosis; A Call for Development of Targeted Therapeutics |
| title_sort | collagen characterization in a model of nonalcoholic steatohepatitis with fibrosis a call for development of targeted therapeutics |
| topic | precision therapeutics NASH fibrosis collagen type I collagen type III transcriptomic |
| url | https://www.mdpi.com/1420-3049/26/11/3316 |
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