Single nucleotide polymorphisms in Tolloid-like 1 (TLL1) and the expression of are known to be closely related to hepatocarcinogenesis after hepatitis C virus elimination or liver fibrosis in patients with nonalcoholic fatty liver disease. TLL1 is a type of matrix metalloprotease and has two isoforms in humans, with the short isoform showing higher activity. However, the functional role of TLL1 in human liver development is unknown. Here, we attempted to elucidate the function of human TLL1 using hepatocyte-like cells generated from human pluripotent stem cells. First, we generated TLL1-knockout human induced pluripotent stem (iPS) cells and found that hepatic differentiation was promoted by TLL1 knockout. Next, we explored TLL1-secreting cells using a model of liver development and identified that kinase insert domain receptor (FLK1)-positive cells (mesodermal cells) highly express TLL1. Finally, to elucidate the mechanism by which TLL1 knockout promotes hepatic differentiation, the expression profiles of transforming growth factor beta (), a main target gene of TLL1, and its related genes were analyzed in hepatic differentiation. Both the amount of active TGFβ and the expression of TGFβ target genes were decreased by TLL1 knockout. It is known that TGFβ negatively regulates hepatic differentiation. TLL1 appears to negatively regulate hepatic differentiation of human iPS cells by up-regulating TGFβ signaling. Our findings will provide new insight into the function of TLL1 in human liver development.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996343 | PMC |
| http://dx.doi.org/10.1002/hep4.1466 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The kinetically-derived maximal dose (KMD) is defined as the maximum external dose at which kinetics are unchanged relative to lower doses, e.g., doses at which kinetic processes are not saturated.
View Article and Find Full Text PDFAutophagy related 7 (ATG7) regulates food intake and liver health during asparaginase exposure.
J Biol Chem
January 2025
Nutritional Sciences Graduate Program, Rutgers University, New Brunswick, New Jersey, United States; Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States; Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey, United States; Endocrinology and Animal Biosciences Graduate Program, Rutgers University, New Brunswick, New Jersey, United States; New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, New Jersey, United States. Electronic address:
Amino acid starvation by the chemotherapy agent asparaginase is a potent activator of the integrated stress response (ISR) in liver and can upregulate autophagy in some cell types. We hypothesized that autophagy related 7 (ATG7), a protein that is essential for autophagy and an ISR target gene, was necessary during exposure to asparaginase to maintain liver health. We knocked down Atg7 systemically (Atg7) or in hepatocytes only (ls-Atg7KO) in mice before exposure to pegylated asparaginase for 5 d.
View Article and Find Full Text PDFRadiological Assessment and Therapeutic Evaluation in Hepatocellular Carcinoma: Differentiation and Treatment Response with Japanese Guidelines.
Cancers (Basel)
December 2024
Department of Radiology, Kansai Medical University, Hirakata 573-1010, Osaka, Japan.
The liver is supplied by a dual blood flow system consisting of the portal vein and hepatic artery. Imaging techniques for diagnosing hepatocellular carcinoma (HCC) have been developed along with blood flow imaging, which visualizes the amount of arterial and portal blood flow. The diagnosis of HCC differentiation is important for early-stage liver cancer screening and determination of treatment strategies.
View Article and Find Full Text PDFThe Complexity and Significance of Fibroblast Growth Factor (FGF) Signaling for FGF-Targeted Cancer Therapies.
Cancers (Basel)
December 2024
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers.
View Article and Find Full Text PDF[Clinical progress in stem cell therapy for end-stage liver disease].
Zhonghua Gan Zang Bing Za Zhi
December 2024
Department of Infectious Disease Medicine, Fifth Medical Center, PLA General Hospital, National Clinical Research Center of Infectious Diseases, Beijing100039, China.
End-stage liver disease includes liver failure and decompensated cirrhosis resulting from various etiologies and often leads to patient mortality due to complications and clinical symptoms such as severe jaundice, ascites, hepatic encephalopathy, coagulopathy, and hepatorenal syndrome. Liver transplantation is currently regarded as the most effective treatment, but its clinical application is limited by the shortage of donors, elevated expenses, and post-transplant rejection. Stem cells are a group of cells with multidirectional differentiation potential and self-renewal ability, which can improve the clinical indicator outcomes through mechanisms such as immunoregulation and promotion of tissue repair in patients with end-stage liver disease.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!