A High-Throughput Cell-Based Luciferase Reporter Assay for Identifying Inhibitors of ASGR1 DOI Open Access
Li‐Ming Gan, Haoyu Zou, Zhaoqi Yang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4590 - 4590

Published: May 10, 2025

The asialoglycoprotein receptor 1 (ASGR1) represents a highly promising target for drug development, with its expression regulation closely linked to various diseases. Consequently, research concentrating on targeted therapies against ASGR1 holds significant importance in devising effective treatment strategies. In this study, we utilized the CRISPR-Knockin technology insert firely luciferase reporter gene downstream of exon 9 HepG2 cell line. This modification enables level be directly proportional activity intensity protein. We successfully established screening and evaluation model employed it high-throughput potential inhibitors from microbial molecular metabolite library. After our process, several candidates were identified as inhibitors. Western blotting experiment was conducted validate efficacy model, thereby providing solid experimental foundation development novel therapeutics targeting ASGR1.

Language: Английский

Serum Soluble Asialoglycoprotein Receptor 1: A Potential Predictor Marker Linked to Type 2 Diabetes Mellitus, Demonstrating Positive Correlation With High Sensitive C-Reactive Protein DOI Creative Commons
Haifeng Zhu, Ziyi Zhong, Gaonian Zhao

et al.

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2025, Volume and Issue: Volume 18, P. 663 - 675

Published: Feb. 1, 2025

Asialoglycoprotein receptor 1 (ASGR1) deficiency has been implicated in enhancing liver insulin sensitivity and reducing systemic resistance, thus highlighting its pivotal role glucose metabolism. However, the association between serum soluble asialoglycoprotein (sASGR1) type 2 diabetes mellitus (T2DM) remains elusive. Therefore, we conducted a study to delve into this association. From July October 2024, 220 newly diagnosed T2DM patients an equal number of matched controls with normal tolerance (NGT) were enrolled. Serum sASGR1 levels quantified using ELISA, carotid artery assessed ultrasound imaging. The median level was significantly higher group (6.58 ng/mL) compared NGT (5.26 ng/mL). Notably, no significant difference observed individuals without atherosclerosis or fatty liver. In group, exhibited positive correlation high-sensitivity C-reactive protein (hs-CRP) interleukin-6 (IL-6). Among patients, positively associated estimated glomerular filtration rate (eGFR), resistance (as measured by HOMA-IR), triglycerides (TG), hs-CRP, but negatively creatinine (Cr). linear regression analysis identified Cr as independent negative factor hs-CRP levels. Logistic indicated that highest had odds developing lowest even after adjusting for potential confounders. significance attenuated further adjustment hs-CRP. area under receiver operating characteristic (ROC) curve 0.610. are elevated correlate demonstrates limited predictive value onset T2DM. Further research is warranted explore renal function, blood lipids, health, arteriosclerosis.

Language: Английский

Citations

0

A High-Throughput Cell-Based Luciferase Reporter Assay for Identifying Inhibitors of ASGR1 DOI Open Access
Li‐Ming Gan, Haoyu Zou, Zhaoqi Yang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4590 - 4590

Published: May 10, 2025

The asialoglycoprotein receptor 1 (ASGR1) represents a highly promising target for drug development, with its expression regulation closely linked to various diseases. Consequently, research concentrating on targeted therapies against ASGR1 holds significant importance in devising effective treatment strategies. In this study, we utilized the CRISPR-Knockin technology insert firely luciferase reporter gene downstream of exon 9 HepG2 cell line. This modification enables level be directly proportional activity intensity protein. We successfully established screening and evaluation model employed it high-throughput potential inhibitors from microbial molecular metabolite library. After our process, several candidates were identified as inhibitors. Western blotting experiment was conducted validate efficacy model, thereby providing solid experimental foundation development novel therapeutics targeting ASGR1.

Language: Английский

Citations

0