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Article: Tocilizumab Exerts Anti-Tumor Effects on Colorectal Carcinoma Cell Xenografts Corresponding to Expression Levels of Interleukin-6 Receptor.

Chung, Yuan-Chiang / Chen, Szu-Jung / Huang, Chiu-Chen / Liu, Wei-Chun / Lai, Ming-Tsung / Kao, Ting-Yu / Yang, Wei-Shun / Yang, Chien-Hui / Hsu, Chih-Ping / Chang, Jia-Feng

Pharmaceuticals (Basel, Switzerland)

2024 Volume 17, Issue 1

Abstract: The use of tocilizumab against the interleukin-6 receptor (IL-6R) has been demonstrated as inhibiting the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of tocilizumab on human colorectal ... ...

Abstract	The use of tocilizumab against the interleukin-6 receptor (IL-6R) has been demonstrated as inhibiting the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of tocilizumab on human colorectal carcinoma (CRC) corresponding to IL-6R expression levels remains scarce. To investigate the influence of IL-6R expression, SW480 and HT-29 cells inoculated subcutaneously into NU/NU mice were used as human CRC xenograft models with anti-IL-6R antibody (tocilizumab) therapy. The IL-6R expression levels, histology of CRC growth/invasiveness, and tumor growth-related signaling pathway were estimated by H&E and immunohistochemical staining. SW480 tumor cells with higher IL-6R expression levels showed better responsiveness in tocilizumab therapy than in the treated HT-29 group. Likewise, therapeutic effects of tocilizumab on the proliferative ability with mitotic index and Ki-67 expressions, invasiveness with MMP-9 proteinase expressions, and ERK 1/2 and STAT3 signaling transduction in the SW480 treatment group were superior to the HT-29 treatment group. In light of our results, IL-6R is the key indicator for the efficacy of tocilizumab treatment in CRC xenografts. From the perspective of precision medicine, tumor response to anti-IL-6R antibody therapy could be predicted on the basis of IL-6R expression levels. In this manner, tocilizumab may serve as a targeted and promising anti-CRC therapy.
Language	English
Publishing date	2024-01-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph17010127
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Article: Risk of major adverse limb events in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A population-based retrospective cohort study.

Lee, Yen-Chieh / Dong, Yaa-Hui / Yang, Wei-Shun / Wu, Li-Chiu / Lin, Jou-Wei / Chang, Chia-Hsuin

Frontiers in pharmacology

2022 Volume 13, Page(s) 869804

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2022-09-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.869804
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Article ; Online: Comparative cardiovascular effectiveness of glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes: A population-based cohort study.

Dong, Yaa-Hui / Chang, Chia-Hsuin / Lin, Jou-Wei / Yang, Wei-Shun / Wu, Li-Chiu / Toh, Sengwee

Diabetes, obesity & metabolism

2022 Volume 24, Issue 8, Page(s) 1623–1637

Abstract: Aims: To examine the comparative effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for select cardiovascular outcomes and to examine whether the relative risks varied across ... ...

Abstract	Aims: To examine the comparative effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for select cardiovascular outcomes and to examine whether the relative risks varied across different patient subgroups in patients with type 2 diabetes. Materials and methods: We conducted a nationwide cohort study of patients with type 2 diabetes who initiated GLP-1RAs or SGLT2 inhibitors between 2012 and 2018 in Taiwan. The study outcomes included myocardial infarction and total stroke, further classified into ischaemic or haemorrhagic stroke. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for each outcome, comparing GLP-1RAs with SGLT2 inhibitors using Cox proportional hazards models after 1:1 propensity-score (PS) matching. We also examined if there was effect modification by age, underlying chronic kidney disease, or coexisting cardiovascular disease in prespecified subgroup analyses. Results: Among 26 032 PS-matched patients, GLP-1RA initiators and SGLT2 inhibitor initiators showed similar risks of myocardial infarction (HR 0.99, 95% CI 0.65-1.52), total stroke (HR 0.90, 95% CI 0.69-1.17), ischaemic stroke (HR 0.86, 95% CI 0.65-1.14) and haemorrhagic stroke (HR 0.88, 95% CI 0.63-1.25). However, GLP-1RA treatment was associated with an increased risk of total stroke (HR 1.76, 95% CI 1.06-2.94) and ischaemic stroke (HR 1.88, 95% CI 1.09-3.23) among patients with chronic kidney disease, but not among patients without chronic kidney disease. GLP-1RA therapy seemed to have a lower risk of haemorrhagic stroke among patients with cardiovascular disease (HR 0.64, 95% CI 0.43-0.97), but not in patients without cardiovascular disease. Conclusions: Glucagon-like peptide-1 receptor agonists and SGLT2 inhibitors appeared to have comparable effectiveness with regard to several cardiovascular outcomes overall, but their comparative effectiveness may vary in certain patient subgroups.
MeSH term(s)	Brain Ischemia ; Cardiovascular Diseases/chemically induced ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/prevention & control ; Cohort Studies ; Diabetes Mellitus, Type 2/chemically induced ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Glucagon-Like Peptide-1 Receptor/agonists ; Glucose ; Hemorrhagic Stroke ; Humans ; Hypoglycemic Agents/therapeutic use ; Ischemic Stroke ; Myocardial Infarction/chemically induced ; Myocardial Infarction/epidemiology ; Myocardial Infarction/prevention & control ; Renal Insufficiency, Chronic/complications ; Sodium ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Stroke/chemically induced ; Stroke/epidemiology ; Stroke/prevention & control
Chemical Substances	Glucagon-Like Peptide-1 Receptor ; Hypoglycemic Agents ; Sodium-Glucose Transporter 2 Inhibitors ; Sodium (9NEZ333N27) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-05-25
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1454944-x
ISSN	1463-1326 ; 1462-8902
ISSN (online)	1463-1326
ISSN	1462-8902
DOI	10.1111/dom.14741
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Zs.A 5442: Show issues

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Article ; Online: GSK3α phosphorylates dynamin-2 to promote GLUT4 endocytosis in muscle cells.

Laiman, Jessica / Hsu, Yen-Jung / Loh, Julie / Tang, Wei-Chun / Chuang, Mei-Chun / Liu, Hui-Kang / Yang, Wei-Shun / Chen, Bi-Chang / Chuang, Lee-Ming / Chang, Yi-Cheng / Liu, Ya-Wen

The Journal of cell biology

2022 Volume 222, Issue 2

Abstract: Insulin-stimulated translocation of glucose transporter 4 (GLUT4) to plasma membrane of skeletal muscle is critical for postprandial glucose uptake; however, whether the internalization of GLUT4 is also regulated by insulin signaling remains unclear. ... ...

Abstract	Insulin-stimulated translocation of glucose transporter 4 (GLUT4) to plasma membrane of skeletal muscle is critical for postprandial glucose uptake; however, whether the internalization of GLUT4 is also regulated by insulin signaling remains unclear. Here, we discover that the activity of dynamin-2 (Dyn2) in catalyzing GLUT4 endocytosis is negatively regulated by insulin signaling in muscle cells. Mechanistically, the fission activity of Dyn2 is inhibited by binding with the SH3 domain of Bin1. In the absence of insulin, GSK3α phosphorylates Dyn2 to relieve the inhibition of Bin1 and promotes endocytosis. Conversely, insulin signaling inactivates GSK3α and leads to attenuated GLUT4 internalization. Furthermore, the isoform-specific pharmacological inhibition of GSK3α significantly improves insulin sensitivity and glucose tolerance in diet-induced insulin-resistant mice. Together, we identify a new role of GSK3α in insulin-stimulated glucose disposal by regulating Dyn2-mediated GLUT4 endocytosis in muscle cells. These results highlight the isoform-specific function of GSK3α on membrane trafficking and its potential as a therapeutic target for metabolic disorders.
MeSH term(s)	Animals ; Mice ; Adaptor Proteins, Signal Transducing ; Dynamin II/metabolism ; Endocytosis ; Glucose ; Glucose Transporter Type 4/metabolism ; Glycogen Synthase Kinase 3/metabolism ; Insulin ; Insulin Resistance ; Muscle Cells/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Bin1 protein, mouse ; Dynamin II (EC 3.6.5.5) ; Glucose (IY9XDZ35W2) ; Glucose Transporter Type 4 ; Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; Insulin ; Slc2a4 protein, mouse ; DNM2 protein, mouse (EC 3.6.5.5)
Language	English
Publishing date	2022-11-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202102119
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Article: The Association Between Body Mass Index and the Risk of Hospitalization and Mortality due to Infection: A Prospective Cohort Study.

Yang, Wei-Shun / Chang, Yi-Cheng / Chang, Chia-Hsuin / Wu, Li-Chiu / Wang, Jiun-Ling / Lin, Hsien-Ho

Open forum infectious diseases

2020 Volume 8, Issue 1, Page(s) ofaa545

Abstract: Background: We aim to determine whether obesity increases the risk of various infections using a large prospective population-based cohort.: Methods: A total of 120 864 adults were recruited from the New Taipei City health screening program from 2005 ...

Abstract	Background: We aim to determine whether obesity increases the risk of various infections using a large prospective population-based cohort. Methods: A total of 120 864 adults were recruited from the New Taipei City health screening program from 2005 to 2008. Statistics for hospitalization and mortality due to infection were obtained from the National Health Insurance Database and the National Death Registry in Taiwan. Results: During a mean follow-up period of 7.61 years, there were 438, 7582, 5298, and 1480 first hospitalizations due to infection in the underweight, normal, overweight, and obese groups, respectively. Obesity significantly increases the risk of hospitalization for intra-abdominal infections (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.00-1.40), including diverticulitis, liver abscess, acute cholecystitis and anal and rectal abscess, reproductive and urinary tract infection (aHR, 1.38; 95% CI, 1.26-1.50), skin and soft tissue infection (aHR, 2.46; 95% CI, 2.15-2.81), osteomyelitis (aHR, 1.70; 95% CI, 1.14-2.54), and necrotizing fasciitis (aHR, 3.54; 95% CI,1.87-6.67), and this relationship is dose-dependent. This study shows that there is a U-shaped association between body mass index (BMI) and hospitalization for lower respiratory tract infection, septicemia, and the summation of all infections and that underweight people are at the greatest risk, followed by obese people. There is a clear negative relationship between BMI and infection-related mortality. Conclusions: The pattern that BMI affects the risk of hospitalization and mortality due to infection varies widely across infection sites. It is necessary to tailor preventive and therapeutic measures against different infections in hosts with different BMIs.
Language	English
Publishing date	2020-10-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofaa545
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Article ; Online: Stratified risks of infection-related hospitalization in patients with chronic kidney disease - A prospective cohort study.

Yang, Wei-Shun / Chang, Yi-Cheng / Hsieh, Meng-Lun / Wang, Jiun-Ling / Wu, Li-Chiu / Chang, Chia-Hsuin

Scientific reports

2020 Volume 10, Issue 1, Page(s) 4475

Abstract: Patients with chronic kidney disease (CKD) are at high risk of infection, but whether the risks are attenuated in different patient groups remains unclear. This study enrolled participants with CKD stages 1-3 in the New Taipei City Health Screening ... ...

Abstract	Patients with chronic kidney disease (CKD) are at high risk of infection, but whether the risks are attenuated in different patient groups remains unclear. This study enrolled participants with CKD stages 1-3 in the New Taipei City Health Screening Program between 2005 and 2008. A proportional hazard regression model was employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for infection-related hospitalization and mortality in younger (<50-year-old) and older (≥50-year-old) CKD patients. Of 119,871 adults, there were 14,207 cases of first hospitalization for infection during a median follow-up of 8.14 years; 45.5% of these cases were younger patients. Unlike CKD stage 1 and 2 patients, the risk of infection-related hospitalization in younger CKD stage 3 patients is as high as for older CKD stage 3 patients. Proteinuria increases the risk of infection-related hospitalization independent of estimated glomerular filtration rate (eGFR) levels in older CKD patients but this relationship is weak in their younger counterparts. In conclusion, the risk of infection-related hospitalization is high in subgroups of CKD patients. Prevention and treatment of infections in these patients merit more attention.
MeSH term(s)	Adult ; Aged ; Comorbidity ; Female ; Hospitalization ; Humans ; Infections/epidemiology ; Infections/etiology ; Kidney Function Tests ; Male ; Middle Aged ; Proportional Hazards Models ; Prospective Studies ; Public Health Surveillance ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/epidemiology ; Risk Assessment ; Risk Factors ; Severity of Illness Index
Language	English
Publishing date	2020-03-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-61144-6
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Article: Deterioration of Deceleration Capacity of Heart Rate is Associated with Left Ventricular Hypertrophy in End-Stage Renal Disease Population.

Lin, Ting-Tse / Yang, Wei-Shun / Hsieh, Mu-Yang / Wu, Chih-Chen / Lin, Lian-Yu

Acta Cardiologica Sinica

2018 Volume 34, Issue 3, Page(s) 242–250

Abstract: Background: Left ventricular hypertrophy (LVH) is prevalent in patients with end-stage renal disease (ESRD), and may be secondary to arterial stiffness and volume overload. It is unclear whether LVH is caused by autonomic nerve dysregulation (AND), a ... ...

Abstract	Background: Left ventricular hypertrophy (LVH) is prevalent in patients with end-stage renal disease (ESRD), and may be secondary to arterial stiffness and volume overload. It is unclear whether LVH is caused by autonomic nerve dysregulation (AND), a frequent condition in patients with ESRD that is characterized by sympathetic hyperactivity and vagal withdrawal. We hypothesized that AND estimated by heart rate variability (HRV) may be associated with LVH in patients with ESRD. Methods: We prospectively enrolled patients with ESRD undergoing hemodialysis. Cardiac function and LVH were assessed using echocardiography according to the recommendations of the American Society of Echocardiography. Holter recordings were used to quantify HRV and deceleration capacity (DC). Dataon comorbidities and medications, and serum markers were obtained. Logistic regression analysis was performed. Results: Among the 281 included patients, 63% had LVH. The patients with LVH were older, had more comorbidities and advanced diastolic dysfunction than those without LVH. The root mean square of successive differences (rMSSD) (9.10 ± 5.44 versus 13.25 ± 8.61; p = 0.004) and DC (2.08 ± 1.90 versus 3.89 ± 1.45; p = 0.021) were lower in the patients with LVH than that in those without LVH. Multivariate regression analysis showed that hypertension, asymmetrical dimethylarginine (ADMA), advanced diastolic dysfunction grade, rMSSD, and DC were independently associated with LVH. Among these variables, DC and ADMA showed the highest diagnostic value for LVH with areas under curves of 0.701 and 0.751, respectively. Conclusions: AND is independently associated with LVH in patients with ESRD.
Language	English
Publishing date	2018-05-29
Publishing country	China (Republic : 1949- )
Document type	Journal Article
ZDB-ID	1051394-2
ISSN	1011-6842
ISSN	1011-6842
DOI	10.6515/ACS.201805_34(3).20180202A
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Article: Remote organ failure in acute kidney injury.

Kao, Chih-Chin / Yang, Wei-Shun / Fang, Ji-Tseng / Liu, Kathleen D / Wu, Vin-Cent

Journal of the Formosan Medical Association = Taiwan yi zhi

2018 Volume 118, Issue 5, Page(s) 859–866

Abstract: Despite supportive care with renal replacement therapy, acute kidney injury (AKI) remains linked with increased short and long-term mortality, not just because of renal failure but also because of accompanying remote organ dysfunction. Increasing ... ...

Abstract	Despite supportive care with renal replacement therapy, acute kidney injury (AKI) remains linked with increased short and long-term mortality, not just because of renal failure but also because of accompanying remote organ dysfunction. Increasing evidence from animal studies suggests that numerous factors contribute both to the development of AKI and the impairment of various vital organs, including pro-inflammatory cytokine expression, leukocyte infiltration, vascular permeability changes, ion channel derangement, oxidative stress, and cell apoptosis. Human studies have reported that AKI with concomitant multi-organ dysfunction is associated with a high death rate. We propose that persistent organ dysfunction after AKI can be considered in relation to three proposed mechanisms (1) classical uremic stress and its associated sequelae (2) systemic inflammation as a consequence of kidney injury (3) treatment-related effects. Using this framework, we discuss the known pathways through which AKI can affect the function of a number of remote organs. We review the short- and long-term clinical impact of AKI on other organ systems and potential mechanisms through which AKI may affect remote organ systems. Further elucidating the effects of AKI on remote organ function may lead to new therapeutic strategies to improve outcomes after AKI.
MeSH term(s)	Acute Kidney Injury/complications ; Acute Kidney Injury/mortality ; Acute Kidney Injury/physiopathology ; Animals ; Apoptosis ; Cytokines/metabolism ; Humans ; Inflammation/physiopathology ; Long Term Adverse Effects/mortality ; Long Term Adverse Effects/physiopathology ; Multiple Organ Failure/etiology ; Multiple Organ Failure/mortality ; Multiple Organ Failure/physiopathology ; Renal Replacement Therapy/adverse effects
Chemical Substances	Cytokines
Language	English
Publishing date	2018-05-21
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2096659-3
ISSN	1876-0821 ; 0929-6646
ISSN (online)	1876-0821
ISSN	0929-6646
DOI	10.1016/j.jfma.2018.04.005
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Article ; Online: Genome-Wide Association Studies for Albuminuria of Nondiabetic Taiwanese Population.

Yang, Wei-Shun / Chuang, Gwo-Tsann / Che, Tony Pan-Hou / Chueh, Li-Yun / Li, Wen-Yi / Hsu, Chih-Neng / Hsiung, Chia-Ni / Ku, Hsiao-Chia / Lin, Yi-Ching / Chen, Yi-Shun / Hee, Siow-Wey / Chang, Tien-Jyun / Chen, Shiau-Mei / Hsieh, Meng-Lun / Lee, Hsiao-Lin / Liao, Karen Chia-Wen / Shen, Chen-Yang / Chang, Yi-Cheng

American journal of nephrology

2023 Volume 54, Issue 9-10, Page(s) 359–369

Abstract: Introduction: Chronic kidney disease, which is defined by a reduced estimated glomerular filtration rate and albuminuria, imposes a large health burden worldwide. Ethnicity-specific associations are frequently observed in genome-wide association studies ...

Abstract	Introduction: Chronic kidney disease, which is defined by a reduced estimated glomerular filtration rate and albuminuria, imposes a large health burden worldwide. Ethnicity-specific associations are frequently observed in genome-wide association studies (GWAS). This study conducts a GWAS of albuminuria in the nondiabetic population of Taiwan. Methods: Nondiabetic individuals aged 30-70 years without a history of cancer were enrolled from the Taiwan Biobank. A total of 6,768 subjects were subjected to a spot urine examination. After quality control using PLINK and imputation using SHAPEIT and IMPUTE2, a total of 3,638,350 single-nucleotide polymorphisms (SNPs) remained for testing. SNPs with a minor allele frequency of less than 0.1% were excluded. Linear regression was used to determine the relationship between SNPs and log urine albumin-to-creatinine ratio. Results: Six suggestive loci are identified in or near the FCRL3 (p = 2.56 × 10-6), TMEM161 (p = 4.43 × 10-6), EFCAB1 (p = 2.03 × 10-6), ELMOD1 (p = 2.97 × 10-6), RYR3 (p = 1.34 × 10-6), and PIEZO2 (p = 2.19 × 10-7). Genetic variants in the FCRL3 gene that encode a secretory IgA receptor are found to be associated with IgA nephropathy, which can manifest as proteinuria. The PIEZO2 gene encodes a sensor for mechanical forces in mesangial cells and renin-producing cells. Five SNPs with a p-value between 5 × 10-6 and 5 × 10-5 are also identified in five genes that may have a biological role in the development of albuminuria. Conclusion: Five new loci and one known suggestive locus for albuminuria are identified in the nondiabetic Taiwanese population.
MeSH term(s)	Humans ; Genome-Wide Association Study ; Albuminuria/genetics ; Albuminuria/epidemiology ; Renal Insufficiency, Chronic ; Kidney Function Tests ; Glomerulonephritis, IGA ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2023-07-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604540-6
ISSN	1421-9670 ; 0250-8095
ISSN (online)	1421-9670
ISSN	0250-8095
DOI	10.1159/000531783
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Article ; Online: ER ribosomal-binding protein 1 regulates blood pressure and potassium homeostasis by modulating intracellular renin trafficking.

Journal of biomedical science

2023 Volume 30, Issue 1, Page(s) 13

Abstract: Background: Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown.: ... ...

Abstract	Background: Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown. Methods: To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model. Results: In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion. Conclusions: RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.
MeSH term(s)	Animals ; Humans ; Mice ; Aldosterone ; Aluminum Oxide ; Blood Pressure ; Genome-Wide Association Study ; Homeostasis ; Hyperkalemia/complications ; Hypertension ; Hypoaldosteronism/complications ; Potassium ; Renin/genetics ; Carrier Proteins/genetics ; Carrier Proteins/physiology
Chemical Substances	Aldosterone (4964P6T9RB) ; Aluminum Oxide (LMI26O6933) ; Potassium (RWP5GA015D) ; Renin (EC 3.4.23.15) ; RRBP1 protein, human ; Carrier Proteins
Language	English
Publishing date	2023-02-19
Publishing country	England
Document type	Journal Article
ZDB-ID	1193378-1
ISSN	1423-0127 ; 1021-7770
ISSN (online)	1423-0127
ISSN	1021-7770
DOI	10.1186/s12929-023-00905-7
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