ArticleProceedings of the National Academy of Sciences of the United States of America2020
Complement C1q mediates the expansion of periportal hepatic progenitor cells in senescence-associated inflammatory liver.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Role of cellular senescence in hepatic diseases (Review).International journal of molecular medicine · 2025Review
- Stem cell-based therapeutic strategies for liver aging.Liver research (Beijing, China) · 2025Review
- Macrophage C1q contributes to pulmonary fibrosis by disturbing the metabolism of alveolar epithelial cells.Clinical and translational medicine · 2025Article
- The Roles of Myeloid Cells in Aging-related Liver Diseases.International journal of biological sciences · 2023Review
- Mechanisms of tumor-associated macrophages affecting the progression of hepatocellular carcinoma.Frontiers in pharmacology · 2023Review
- Proteomic analysis of small extracellular vesicles from the plasma of patients with hepatocellular carcinoma.World journal of surgical oncology · 2022Article
- The Complement System: A Potential Therapeutic Target in Liver Cancer.Life (Basel, Switzerland) · 2022Review
- An update on the role of complement in hepatocellular carcinoma.Frontiers in immunology · 2022Review
- Unique Features of Hepatitis B Virus-Related Hepatocellular Carcinoma in Pathogenesis and Clinical Significance.Cancers · 2021Review
- "Complimenting the Complement": Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most hepatocellular carcinomas (HCCs) develop in patients with chronic hepatitis, which creates a microenvironment for the growth of hepatic progenitor cells (HPCs) at the periportal area and subsequent development of HCCs. We investigated the signal from the inflammatory liver for this pathogenic process in the hepatic conditional β-catenin knockout mouse model. Senescent β-catenin-depleted hepatocytes in aged mice create an inflammatory microenvironment that stimulates periportal HPC expansion but arrests differentiation, which predisposes mice to the development of liver tumors. The release of complement C1q from macrophages in the inflammatory niche was identified as the unorthodox signal that activated the β-catenin pathway in periportal HPCs and was responsible for their expansion and de-differentiation. C1q inhibitors blocked the β-catenin pathway in both the expanding HPCs and the liver tumors but spared its orthodox pathway in pericentral normal hepatocytes. This mechanism has been validated in human liver specimens from patients with chronic hepatitis. Taken together, these results demonstrate that C1q- mediated activation of β-catenin pathway in periportal HPCs is a previously unrecognized mechanism for replenishing hepatocytes in the inflammatory liver and, if unchecked, for promoting hepatocarcinogenesis. C1q may become a new target for blocking carcinogenesis in patients with chronic hepatitis.
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