ArticleThe Journal of biological chemistry2019
Cell surface expression of 78-kDa glucose-regulated protein (GRP78) mediates diabetic nephropathy.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review).Molecular medicine reports · 2026Review
- Inhibition of cell surface GRP78 and activated α2M interaction attenuates kidney fibrosis.JCI insight · 2025Article
- Metformin attenuates endoplasmic reticulum stress in diabetic kidney disease: mechanistic insights and future perspectives.International urology and nephrology · 2025Review
- Endoplasmic reticulum stress as a driver and therapeutic target for kidney disease.Nature reviews. Nephrology · 2025Review
- Modulators of Alpha-2 Macroglobulin Upregulation by High Glucose in Glomerular Mesangial Cells.Biomolecules · 2024Article
- The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19.International journal of molecular sciences · 2024Review
- Expression of Autophagy Markers LC3B, LAMP2A, and GRP78 in the Human Kidney during Embryonic, Early Fetal, and Postnatal Development and Their Significance in Diabetic Kidney Disease.International journal of molecular sciences · 2024Article
- Endoplasmic reticulum stress in diabetic kidney disease: adaptation and apoptosis after three UPR pathways.Apoptosis : an international journal on programmed cell death · 2023Review
- The Angiogenesis Inhibitor Isthmin-1 (ISM1) Is Overexpressed in Experimental Models of Glomerulopathy and Impairs the Viability of Podocytes.International journal of molecular sciences · 2023Article
- Cell surface GRP78 regulates TGFβ1-mediated profibrotic responsesFrontiers in pharmacology · 2023Article
- Integrin β1/Cell Surface GRP78 Complex Regulates TGFβ1 and Its Profibrotic Effects in Response to High Glucose.Biomedicines · 2022Article
- Naringenin alleviates hyperglycemia-induced renal toxicity by regulating activating transcription factor 4-C/EBP homologous protein mediated apoptosis.Journal of cell communication and signaling · 2022Article
- Circulating TRB3 and GRP78 levels in type 2 diabetes patients: crosstalk between glucose homeostasis and endoplasmic reticulum stress.Journal of endocrinological investigation · 2022Article
- The IRE1α pathway in glomerular diseases: The unfolded protein response and beyond.Frontiers in molecular medicine · 2022Review
- Activated Alpha 2-Macroglobulin Is a Novel Mediator of Mesangial Cell Profibrotic Signaling in Diabetic Kidney Disease.Biomedicines · 2021Article
- ER residential chaperone GRP78 unconventionally relocalizes to the cell surface via endosomal transport.Cellular and molecular life sciences : CMLS · 2021Article
- Activin A and Cell-Surface GRP78 Are Novel Targetable RhoA Activators for Diabetic Kidney Disease.International journal of molecular sciences · 2021Article
- PERK-Dependent Activation of the JAK2/STAT3 Pathway Contributes to High Glucose-Induced Extracellular Matrix Deposition in Renal Tubular Epithelial Cells.International journal of endocrinology · 2021Article
- Host-Pathogen Molecular Factors Contribute to the Pathogenesis ofCurrent tropical medicine reports · 2021Review
- Calreticulin is important for the development of renal fibrosis and dysfunction in diabetic nephropathy.Matrix biology plus · 2020Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The 78-kDa glucose-regulated protein (GRP78) is a well-established endoplasmic reticulum (ER)-resident chaperone that maintains protein homeostasis and regulates the unfolded protein response. Under conditions of ER stress, GRP78 is also expressed at the cell surface and implicated in tumorigenesis, immunity, and cellular signaling events. The role of cell surface-associated GRP78 (csGRP78) in the pathogenesis of diabetic nephropathy has not yet been defined. Here we explored the role of csGRP78 in regulating high glucose (HG)-induced profibrotic AKT Ser/Thr kinase (AKT) signaling and up-regulation of extracellular matrix proteins. Using primary kidney mesangial cells, we show that HG treatment, but not the osmotic control mannitol, induces csGRP78 expression through an ER stress-dependent mechanism. We found that csGRP78, known to be located on the outer membrane leaflet, interacts with the transmembrane protein integrin β1 and activates focal adhesion kinase and downstream PI3K/AKT signaling. Localization of GRP78 at the cell surface and its interaction with integrin β1 were also required for extracellular matrix protein synthesis in response to HG. Surprisingly, both the N and C termini of csGRP78 were necessary for this profibrotic response. Increased localization of GRP78 at the plasma membrane was also found in the glomerular mesangial area of type 1 diabetic mice in two different models (streptozotocin-induced and Akita). In freshly isolated glomeruli from Akita mice, csGRP78 co-localized with the mesangial cell surface marker α8-integrin. In conclusion, our work reveals a role for csGRP78 in HG-induced profibrotic responses in mesangial cells, informing a potential approach to treating diabetic nephropathy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.