Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectives
Background and purpose: Liver fibrosis, a progressive liver disease arising from viral or metabolic causes, poses a major global health challenge due to its potential progression to cirrhosis and hepatocellular carcinoma. Due to the complex aetiology and epidemiology of liver fibrosis, most therapi...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
International Association of Physical Chemists (IAPC)
2025-08-01
|
| Series: | ADMET and DMPK |
| Subjects: | |
| Online Access: | https://pub.iapchem.org/ojs/index.php/admet/article/view/2874 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849239370996908032 |
|---|---|
| author | Alka Singh Ansab Akhtar Prashant Shukla |
| author_facet | Alka Singh Ansab Akhtar Prashant Shukla |
| author_sort | Alka Singh |
| collection | DOAJ |
| description |
Background and purpose: Liver fibrosis, a progressive liver disease arising from viral or metabolic causes, poses a major global health challenge due to its potential progression to cirrhosis and hepatocellular carcinoma. Due to the complex aetiology and epidemiology of liver fibrosis, most therapies fail in the clinic, and very few drugs have been approved by the US FDA. Approach: This review highlights the pathophysiological features of liver fibrosis, with a focus on novel targets in hepatic stellate cells (HSCs), key players in the fibrogenesis process, to develop successful therapeutic approaches using both pharmacological agents and active targeting strategies. The review also examines current therapeutic strategies targeting liver fibrosis, both in preclinical lab setups and clinical trials. Furthermore, various receptors involved in HSC-mediated liver fibrosis and active drug delivery targeting strategies are reviewed to enhance therapeutic outcomes. This article also integrates existing knowledge to identify research gaps and guide future investigations and clinical translation in liver fibrosis treatment. In addition, novel pathways pertaining to liver fibrosis, such as the RSPO3-LGR4/5-β-catenin cascade, the CD47/YAP/TEAD4 signalling axis, and HAb18G/CD147, are briefly elaborated in the context of therapeutic approaches for arresting HSC activation. Single-cell RNA sequencing of HSCs is presented to provide a clearer picture of liver fibrosis. Conclusion: The review highlights critical research gaps in liver fibrosis therapy and promising active targeting strategies and pharmacological interventions to improve therapeutic outcomes. Overall, this review provides a robust foundation for scientists and clinicians to advance active targeting of the disease pathology and to develop new pharmaceutical formulations that are pharmacologically safer and more efficacious.
|
| format | Article |
| id | doaj-art-5ae7d601faa945a6a564132cfccaccc1 |
| institution | Kabale University |
| issn | 1848-7718 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | International Association of Physical Chemists (IAPC) |
| record_format | Article |
| series | ADMET and DMPK |
| spelling | doaj-art-5ae7d601faa945a6a564132cfccaccc12025-08-20T04:01:01ZengInternational Association of Physical Chemists (IAPC)ADMET and DMPK1848-77182025-08-0113410.5599/admet.2874Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectivesAlka Singh0https://orcid.org/0009-0005-8145-7794Ansab Akhtar1https://orcid.org/0000-0002-4839-4454Prashant Shukla2https://orcid.org/0000-0003-1286-4183Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Dehradun, IndiaLouisiana State University, Health Sciences Center, New Orleans, United StatesDepartment of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Dehradun, India Background and purpose: Liver fibrosis, a progressive liver disease arising from viral or metabolic causes, poses a major global health challenge due to its potential progression to cirrhosis and hepatocellular carcinoma. Due to the complex aetiology and epidemiology of liver fibrosis, most therapies fail in the clinic, and very few drugs have been approved by the US FDA. Approach: This review highlights the pathophysiological features of liver fibrosis, with a focus on novel targets in hepatic stellate cells (HSCs), key players in the fibrogenesis process, to develop successful therapeutic approaches using both pharmacological agents and active targeting strategies. The review also examines current therapeutic strategies targeting liver fibrosis, both in preclinical lab setups and clinical trials. Furthermore, various receptors involved in HSC-mediated liver fibrosis and active drug delivery targeting strategies are reviewed to enhance therapeutic outcomes. This article also integrates existing knowledge to identify research gaps and guide future investigations and clinical translation in liver fibrosis treatment. In addition, novel pathways pertaining to liver fibrosis, such as the RSPO3-LGR4/5-β-catenin cascade, the CD47/YAP/TEAD4 signalling axis, and HAb18G/CD147, are briefly elaborated in the context of therapeutic approaches for arresting HSC activation. Single-cell RNA sequencing of HSCs is presented to provide a clearer picture of liver fibrosis. Conclusion: The review highlights critical research gaps in liver fibrosis therapy and promising active targeting strategies and pharmacological interventions to improve therapeutic outcomes. Overall, this review provides a robust foundation for scientists and clinicians to advance active targeting of the disease pathology and to develop new pharmaceutical formulations that are pharmacologically safer and more efficacious. https://pub.iapchem.org/ojs/index.php/admet/article/view/2874Retinoid receptorsnon-alcoholic fatty liver diseaseresmetiromliposomesactive targetingclinical trials |
| spellingShingle | Alka Singh Ansab Akhtar Prashant Shukla Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectives ADMET and DMPK Retinoid receptors non-alcoholic fatty liver disease resmetirom liposomes active targeting clinical trials |
| title | Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectives |
| title_full | Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectives |
| title_fullStr | Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectives |
| title_full_unstemmed | Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectives |
| title_short | Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectives |
| title_sort | exploring hepatic stellate cell driven fibrosis therapeutic advances and future perspectives |
| topic | Retinoid receptors non-alcoholic fatty liver disease resmetirom liposomes active targeting clinical trials |
| url | https://pub.iapchem.org/ojs/index.php/admet/article/view/2874 |
| work_keys_str_mv | AT alkasingh exploringhepaticstellatecelldrivenfibrosistherapeuticadvancesandfutureperspectives AT ansabakhtar exploringhepaticstellatecelldrivenfibrosistherapeuticadvancesandfutureperspectives AT prashantshukla exploringhepaticstellatecelldrivenfibrosistherapeuticadvancesandfutureperspectives |