scholarly journals Lipoprotein Glomerulopathy-Like Lesions in Atherosclerotic Mice Defected With HDL Receptor SR-B1

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiawei Liao ◽  
Jie Bai ◽  
Xiangbo An ◽  
Yang Liu ◽  
Yuhui Wang ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Chow Diet ◽  
Loss Of Function ◽  
Lipoprotein Glomerulopathy ◽  
Class B ◽  
Density Lipoprotein Receptor ◽  
Accelerate Atherosclerosis

High-density lipoprotein (HDL) homeostasis is important in maintaining both cardiovascular and renal health. Scavenger receptor class B type 1 (SR-B1), the major HDL receptor in mammals, plays a crucial role in reverse cholesterol transport and HDL metabolism. Evidence from mouse study has well demonstrated that HDL disorders caused by Srb1 inactivation accelerate atherosclerosis and even induce lethal cardiovascular diseases. However, the renal consequences of Srb1 dysfunction are still unknown. Here we explored this issue in both Srb1 knockout (Srb1-/-) mice and atherosclerotic low-density lipoprotein receptor knockout (Ldlr-/-) mice with Srb1 deletion. Our data showed that no apparent renal damage was observed in 5-month-old Srb1-/- mice fed on standard rodent chow diet as well as Srb1-/- mice fed on a high-fat diet (HFD) for 12 weeks. However, 5-month-old Srb1/Ldlr-/- mice fed on rodent chow had increased urinary albumin excretion and developed spontaneous intraglomerular Oil-red O (ORO)-positive lipoprotein deposition that is similar to lesions observed in human lipoprotein glomerulopathy (LPG). HFD feeding accelerated LPG-like lesions in Srb1/Ldlr-/- mice, inducing severe proteinuria and significantly promoting intraglomerular ORO-positive lipoprotein deposition. Interestingly, probucol reversed HFD-induced HDL disorders and almost fully abrogated LPG-like lesions in Srb1/Ldlr-/- mice. In conclusion, the present study demonstrates that SR-B1 dysfunction leads to LPG-like lesions in atherosclerotic mice, which could be rescued by probucol. SR-B1 loss-of-function mutant carriers therefore might be susceptible to developing metabolic nephropathy in addition to cardiovascular diseases, and probucol might be a potential therapeutics.

scholarly journals Scavenger Receptor Class B Type I Is More Conducive to Hepatitis C Virus Invasion Compared with Low-Density Lipoprotein Receptor

2020 ◽  
Author(s):  
Xiangyi Cao ◽  
Qiong Kang ◽  
Deng Jiang ◽  
Jun Xiao ◽  
Yanyu Zhang ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Type I ◽  
Lipoprotein Receptor ◽  
Scavenger Receptor Class ◽  
Recombinant Cells ◽  
Class B ◽  
Density Lipoprotein Receptor

Abstract Background: Hepatitis C virus is the major cause of chronic hepatitis which may deteriorate into liver cirrhosis or hepatocellular carcinoma. A number of studies have demonstrated that HCV cell entry is a complex multi-step process involving several cellular proteins, such as scavenger receptor class B type I (SR-BI), tetraspanin CD81, tight junction protein claudin-1 (CLDN-1) and occludin (OCLN). The low-density lipoprotein receptor (LDLR) is an important factor during the initial HCV particle-binding step, which interacts with the complex formed between the virus particle and the lipoprotein in the blood. However, the process of HCV early infection is not well-established, with many details remaining to be elucidated.This research aimed to study the early entry stage of HCV virus particles and the role of LDLR more effectively.Methods: Recombinant murine cell models of HCV infection in vitro was constructed, that expressed human HCV receptors, such as LDLR, CD81, SR BI, CLDN-1, and OCLN. These factors were also introduced to mice by hydrodynamic delivery to construct a humanized mouse model of HCV infection in vivo.Expression levels of the mRNA of HCV entry factors in recombinant cells were measured by qRT-PCR.Western blotting was used to determine whether the recombinant cells successfully expressed cellular proteins. HCV RNA was assayed by q-PCR following the incublation of HCVsd and HCVcc with the transgenice.Results: Transgenic murine cell lines and mice were developed successfully, and expressed four or five human HCV entry factors in tandem or individually, respectively. We found that all of these transgenic cells and mice were susceptible to HCV, and five entry factors (5EF) rendered higher infectivity. Additionally, we observed that four entry factors (4EF/hLDLR-) could facilitate abundant HCV entry, but four other factors (4EF/hSR-BI-) were less effective.Conclusions: Whether in vitro or in vivo, SR-BI is an essential factor in HCV invasion, and target cells and mice were more vulnerable to the virus in the presence of SR-BI than LDLR. These results suggested that SR-BI may be a potential drug target to inhibit HCV early infection, and the absence of LDLR could reduce the infectivity to the virus.

scholarly journals Effect of estrogen on scavenger receptor BI expression in the rat

2002 ◽  
Vol 175 (3) ◽  
pp. 663-672 ◽  
Author(s):  
H Stangl ◽  
GA Graf ◽  
L Yu ◽  
G Cao ◽  
K Wyne
Keyword(s):  
Ethinyl Estradiol ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
High Dose ◽  
Estradiol Treatment ◽  
Scavenger Receptor Bi ◽  
Class B ◽  
Density Lipoprotein Receptor ◽  
Hypophysectomized Rats

High-dose 17alpha-ethinyl estradiol treatment is associated with increased adrenal and decreased hepatic levels of scavenger receptor class B type 1 (SR-BI) in rats. In this paper we explored the mechanisms responsible for the differential regulation of SR-BI by estrogen in these two tIssues. Previously it was shown that estrogen-treated rats are profoundly hypolipidemic due to increased hepatic low density lipoprotein receptor (LDLR) activity, and that this effect is not maintained with hypophysectomy. To determine if the reduction in hepatic SR-BI was a direct or indirect effect of estrogen, we treated hypophysectomized rats with high-dose estrogen; the levels of SR-BI expression did not change in the livers or adrenals of these animals. To determine if the absence of response to estrogen in the adrenals of hypophysectomized animals was due to the absence of adrenocorticotropic hormone (ACTH), we examined the effect of estrogen treatment on SR-BI expression in animals treated with dexamethasone, which inhibits endogenous ACTH production. The administration of dexamethasone completely inhibited the increase in SR-BI expression in the adrenals of estrogen-treated rats. From these studies we conclude that estrogen does not have a direct effect on SR-BI expression in either the liver or the adrenals. In the liver, the decrease in SR-BI is dependent on the estrogen-induced increase in LDLR activity, and in the adrenal glands, ACTH is required for the estrogen-associated increase in expression of SR-BI.

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