ArticleThe American journal of pathology2011
Mesangial cell integrin αvβ8 provides glomerular endothelial cell cytoprotection by sequestering TGF-β and regulating PECAM-1.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 58 citations in OpenAlex.
- Glomerulo-Tubular Crosstalk in Diabetic Kidney Disease: From Pathophysiology to Novel Therapeutics.Electrolyte & blood pressure : E & BP · 2026Review
- PAX gene expression in autosomal dominant polycystic kidney disease contributes to cyst expansion and regulates a gene network associated with cyst growth.Human molecular genetics · 2026Article
- Integrins in the kidney - beyond the matrix.Nature reviews. Nephrology · 2025Review
- Mesangial Cells in Diabetic Kidney Disease: From Mechanisms to Therapeutic Implications.International journal of biological sciences · 2025Review
- Specificity of endothelial cells in endothelial dysfunction of diabetic kidney disease and their crosstalk with neighboring cells: an updated review.Frontiers in endocrinology · 2025Review
- Investigating the inflammatory mechanism of notoginsenoside R1 in Diabetic nephropathy via ITGB8 based on network pharmacology and experimental validation.Molecular medicine (Cambridge, Mass.) · 2024Article
- Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review.Cell communication and signaling : CCS · 2024Review
- Cellular cross-talk drives mesenchymal transdifferentiation in diabetic kidney disease.Frontiers in medicine · 2024Review
- Cellular crosstalk of mesangial cells and tubular epithelial cells in diabetic kidney disease.Cell communication and signaling : CCS · 2023Review
- MicroRNA-339-5p inhibits lipopolysaccharide-induced rat mesangial cells by regulating the Syk/Ras/c-Fos pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Glomerular cell cross talk in diabetic kidney diseases.Journal of diabetes · 2022Review
- Article
- Ventricular arrhythmias in mouse models of diabetic kidney disease.Scientific reports · 2021Article
- Recessive Mutations inKidney international reports · 2021Article
- Glomerular Endothelial Cells Are the Coordinator in the Development of Diabetic Nephropathy.Frontiers in medicine · 2021Article
- The Glomerulus According to the Mesangium.Frontiers in medicine · 2021Review
- Single Cell Transcriptome Helps Better Understanding Crosstalk in Diabetic Kidney Disease.Frontiers in medicine · 2021Review
- Tracking a TGF-β activator in vivo: sensitive PET imaging of αvβ8-integrin with the Ga-68-labeled cyclic RGD octapeptide trimer Ga-68-Triveoctin.EJNMMI research · 2020Article
- Fatty acid transport protein-2 regulates glycemic control and diabetic kidney disease progression.JCI insight · 2020Article
- αvβ8 integrin adhesion and signaling pathways in development, physiology and disease.Journal of cell science · 2020Review
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10 authors at 5 institutions in 1 country.
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Abstract
Integrins are heterodimeric receptors that regulate cell adhesion, migration, and apoptosis. Integrin αvβ8 is most abundantly expressed in kidney and brain, and its major ligand is latent transforming growth factor-β (TGF-β). Kidney αvβ8 localizes to mesangial cells, which appose glomerular endothelial cells and maintain glomerular capillary structure by mechanical and poorly understood paracrine mechanisms. To establish kidney αvβ8 function, mice with homozygous Itgb8 deletion (Itgb8(-/-)) were generated on outbred and C57BL/6 congenic backgrounds. Most Itgb8(-/-) mice died in utero, and surviving Itgb8(-/-) mice failed to gain weight, and rarely survived beyond 6 weeks. A renal glomerular phenotype included azotemia and albuminuria, as well as increased platelet endothelial cell adhesion molecule-1 (PECAM-1) expression, which was surprisingly not associated with conventional functions, such as endothelial cell hyperplasia, hypertrophy, or perivascular inflammation. Itgb8(-/-) mesangial cells demonstrated reduced latent TGF-β binding, resulting in bioactive TGF-β release, which stimulated glomerular endothelial cell apoptosis. Using PECAM-1 gain and loss of function strategies, we show that PECAM-1 provides endothelial cytoprotection against mesangial cell TGF-β. These results clarify a singular mechanism of mesangial-to-endothelial cell cross-talk, whereby mesangial cell αvβ8 homeostatically arbitrates glomerular microvascular integrity by sequestering TGF-β in its latent conformation. Under pathological conditions associated with decreased mesangial cell αvβ8 expression and TGF-β secretion, compensatory PECAM-1 modulation facilitates glomerular endothelial cell survival.
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