| 2022 |
ASGR1 deficiency decreases lipid levels by stabilizing LXRα: loss of ASGR1 blocks endocytosis and lysosomal degradation of glycoproteins, reduces lysosomal amino-acid levels, inhibits mTORC1 and activates AMPK. AMPK then (1) increases LXRα by decreasing its ubiquitin ligases BRCA1/BARD1, and (2) suppresses SREBP1. LXRα upregulates ABCA1 and ABCG5/G8, promoting cholesterol transport to HDL and excretion to bile/faeces. Anti-ASGR1 neutralizing antibody recapitulates this effect and shows synergy with atorvastatin or ezetimibe. |
Asgr1-knockout mouse model, anti-ASGR1 neutralizing antibody treatment, Western blot, pathway rescue experiments (AMPK inhibition, BRCA1/BARD1 modulation), in vitro and in vivo cholesterol/lipid measurements |
Nature |
High |
35922515
|
| 2021 |
ASGR1 deficiency reduces VLDL/LDL secretion and increases uptake via decreased expression of MTTP and PCSK9 (SREBP targets), linked to increased INSIG1 that traps SREBPs in the ER and prevents their nuclear translocation. INSIG1 knockdown independently reversed ASGR1-deficient lipid phenotypes, establishing an ASGR1/INSIG1/SREBP axis in lipid homeostasis. |
Asgr1-knockout mice, INSIG1 overexpression and knockdown in multiple cell/animal models, SREBP nuclear fractionation, apolipoprotein B secretion assay, LDL uptake assay |
JCI insight |
High |
34622799
|
| 2024 |
ASGR1 binds the ER-stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73, which then interacts with BIP to activate ER stress, leading to liver injury. Neutralization of GP73 attenuates ASGR1 deficiency-induced liver injury. |
Co-IP (ASGR1–GP73 interaction), ASGR1 KO and overexpression mouse models (acetaminophen-induced acute and CCl4-induced chronic injury), GP73 neutralizing antibody, Western blot for ER stress markers |
Nature communications |
High |
38459023
|
| 2021 |
ASGR1 and KREMEN1 are sufficient for ACE2-independent SARS-CoV-2 entry in vitro and in vivo; they were identified by screening 5054 human membrane proteins for interaction with the SARS-CoV-2 spike (S) protein. SARS-CoV-2 uses distinct ACE2/ASGR1/KREMEN1 (ASK) receptor combinations to enter different cell types. |
Genomic receptor profiling screen (5054 membrane proteins), S-protein binding assays, pseudovirus and live-virus entry assays in vitro and in vivo, neutralizing antibody blockade in human lung organoids |
Cell research |
High |
34837059
|
| 2024 |
ASGR1 deficiency reduces VLDL production by inhibiting MTTP and ANGPTL3/ANGPTL8, increases LPL activity, increases LDL uptake via elevated LDLR, and promotes cholesterol efflux through upregulation of LXRα, ABCA1, ABCG5, and CYP7A1. Conversely, ASGR1 overexpression augments VLDL production and reduces fecal cholesterol. Confirmed in both KO and overexpression mouse models on ApoE background. |
Asgr1/ApoE double-KO mice, ASGR1-overexpressing ApoE mice, Western diet feeding, VLDL production assay, LPL activity assay, fecal cholesterol measurement, hepatic gene expression analysis |
Arteriosclerosis, thrombosis, and vascular biology |
High |
39387120
|
| 2021 |
ASGR1 deficiency in pigs reduces hepatic de novo cholesterol synthesis by downregulating HMGCR and increases cholesterol clearance by upregulating LDLR, together lowering non-HDL-C. CRISPR/Cas9-generated ASGR1-deficient pigs on atherogenic diet show lower non-HDL-C and less atherosclerotic lesions. |
CRISPR/Cas9-generated ASGR1-deficient pigs, atherogenic diet feeding, hepatic transcriptome analysis, in vivo cholesterol metabolism tracing |
PLoS genetics |
High |
34762653
|
| 2011 |
ASGR1 on porcine liver sinusoidal endothelial cells mediates binding and phagocytosis of human platelets. siRNA knockdown of ASGR1 reduced its protein by ~20%, correlating with a 21% decrease in human platelet binding. Anti-ASGR1 antibodies and the ASGR1 substrate asialofetuin inhibited platelet binding in a dose-dependent manner. |
siRNA knockdown, anti-ASGR1 inhibition assay, substrate competition with asialofetuin, flow cytometry, quantitative PCR, immunoblot, confocal microscopy |
Xenotransplantation |
Medium |
21848542
|
| 2023 |
ASGR1 promotes monocyte-to-macrophage differentiation by upregulating CD68, F4/80, and CD86. Mechanistically, ASGR1 increases ATF5 expression by promoting phosphorylation of NF-κB and IKBα. ASGR1 physically interacts with ATF5 (demonstrated by co-IP). ASGR1 knockdown in mice suppressed inflammatory monocytes and macrophages in liver and improved survival in LPS-induced sepsis. |
ASGR1 knockdown/overexpression in THP-1 cells and BMDMs, flow cytometry, RNA-seq, co-IP (ASGR1–ATF5), Western blot (NF-κB and IKBα phosphorylation), ASGR1-knockdown mouse LPS sepsis model |
Life sciences |
Medium |
36621538
|
| 2024 |
Paraoxonase-2 (PON2) interacts with ASGR1 and promotes its degradation in a dose-dependent manner, as identified by immunoprecipitation combined with mass spectrometry (IP-MS). PON2-mediated ASGR1 degradation reduced lipid levels in mice. |
IP-MS (immunoprecipitation + mass spectrometry), dose-dependent co-expression experiments, lipid level measurement in mice |
iScience |
Medium |
39055948
|
| 2025 |
ASGR1 (lectin) and DC-SIGN, acting jointly with TMEM106B, allow ACE2-independent entry of SARS-CoV-2 spike mutant E484D. ASGR1 alone or TMEM106B alone was insufficient; the combination directed viral entry to an ACE2-independent, TMEM106B-dependent endosomal pathway that is not inhibited by the neutralizing antibody imdevimab. |
S protein-pseudotyped particle entry assays, cell lines with single and combinatorial expression of ASGR1/DC-SIGN/TMEM106B, imdevimab neutralization assay |
Journal of virology |
Medium |
39791910
|
| 2024 |
ASGR1 deficiency improved hepatic insulin sensitivity in HFD-fed mice, evidenced by enhanced PI3K-AKT insulin signaling in liver (but not muscle or adipose tissue), reduced hepatic gluconeogenesis and glycogenolysis. ASGR1−/− HepG2 cells showed enhanced insulin signal transduction, and transcriptome analysis showed enrichment in PI3K-AKT signaling. |
ASGR1-KO mice fed HFD, ASGR1−/− HepG2 cells, insulin tolerance tests, insulin signaling pathway assays (phospho-AKT), transcriptome analysis, glucose/glycogen metabolism assays |
Diabetes & metabolism journal |
Medium |
38310881
|
| 2024 |
ASGR1 deficiency in ALI exacerbates liver injury via the NOXs-ROS-PANoptosis-like axis: ASGR1 KO hepatocytes show elevated ROS and reduced mitochondrial membrane potential under LPS/D-Gal challenge, activating apoptosis (BAX/BCL-2, cleaved caspase-8) and necroptosis (p-RIPK1, p-RIPK3, p-MLKL). Inhibiting NOXs or scavenging ROS reversed these effects. |
ASGR1-KO mice (LPS/D-Gal ALI model), primary hepatocyte KO/overexpression, cell death inhibitors, ROS inhibitor NAC and NOXs inhibitor DPI, electron microscopy, proteomics, Western blot |
Life sciences |
Medium |
41443470
|
| 2026 |
The natural polyketide enterocin directly binds ASGR1 and promotes its proteasomal (not lysosomal) degradation, leading to AMPKα activation and LXRα-mediated upregulation of cholesterol efflux transporters (ABCA1/G1/G5/G8) in liver cells and in HFD-fed mice. |
Direct binding assay (enterocin–ASGR1), proteasomal vs. lysosomal inhibitor experiments, AMPKα/LXRα/ABCA1/G1/G5/G8 protein/RNA assays, ASGR1 KO and HFD mouse models |
Metabolism: clinical and experimental |
Medium |
41580117
|
| 2000 |
The mouse ASGR1 gene comprises eight coding exons; a minimal 600 bp proximal upstream region exhibits hepatic-specific promoter activity in HepG2 cells, establishing the basis for liver-restricted expression of this receptor. |
Gene sequencing, exon mapping, promoter-reporter assay in HepG2 cells |
Gene |
Low |
10675034
|