5 results on '"FCER1"'
Search Results
2. FcER1 : A Novel Molecule Implicated in the Progression of Human Diabetic Kidney Disease.
- Author
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Sur, Swastika, Nguyen, Mark, Boada, Patrick, Sigdel, Tara K., Sollinger, Hans, and Sarwal, Minnie M.
- Subjects
MONONUCLEAR leukocytes ,DIABETIC nephropathies ,DRUG design ,DISEASE progression ,RENAL biopsy ,DOWNLOADING - Abstract
Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p < 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p < 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
3. FcER1: A Novel Molecule Implicated in the Progression of Human Diabetic Kidney Disease
- Author
-
Swastika Sur, Mark Nguyen, Patrick Boada, Tara K. Sigdel, Hans Sollinger, and Minnie M. Sarwal
- Subjects
diabetes ,DKD ,FcER1 ,chronic kidney disease ,mast cells ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p < 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p < 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.
- Published
- 2021
- Full Text
- View/download PDF
4. FcER1: A Novel Molecule Implicated in the Progression of Human Diabetic Kidney Disease
- Author
-
Minnie M. Sarwal, Patrick Boada, Hans W. Sollinger, Tara K. Sigdel, Mark Nguyen, and Swastika Sur
- Subjects
Male ,Kidney Disease ,FcER1 ,mast cells ,Kidney ,Cohort Studies ,DKD ,Receptors ,Leukocytes ,Immunology and Allergy ,2.1 Biological and endogenous factors ,Diabetic Nephropathies ,Gene Regulatory Networks ,Aetiology ,Oligonucleotide Array Sequence Analysis ,Original Research ,medicine.diagnostic_test ,diabetes ,Middle Aged ,Immunohistochemistry ,medicine.anatomical_structure ,Medical Microbiology ,Disease Progression ,Female ,IgE ,medicine.symptom ,Signal Transduction ,Biotechnology ,Adult ,Mononuclear ,Immunology ,Renal and urogenital ,Inflammation ,Peripheral blood mononuclear cell ,Downregulation and upregulation ,Diabetes mellitus ,Biopsy ,medicine ,Genetics ,Humans ,Metabolic and endocrine ,Aged ,business.industry ,Gene Expression Profiling ,RC581-607 ,medicine.disease ,Cancer research ,Albuminuria ,Immunologic diseases. Allergy ,business ,chronic kidney disease - Abstract
Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p < 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p < 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.
- Published
- 2021
5. Mutual interaction of Basophils and T cells in chronic inflammatory diseases
- Author
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Keiko Wakahara, Marika Sarfati, Laurence Chapuy, and Guy Delespesse
- Subjects
lcsh:Immunologic diseases. Allergy ,Mini Review ,Immunology ,chemical and pharmacologic phenomena ,Immunoglobulin E ,Allergic inflammation ,chemistry.chemical_compound ,Immune system ,Th2 Cells ,memory T cells ,Medicine ,Immunology and Allergy ,Innate immune system ,biology ,business.industry ,FCER1 ,Innate lymphoid cell ,Inflammatory Bowel Diseases ,Basophils ,Interleukin 33 ,chemistry ,biology.protein ,Th17 Cells ,business ,lcsh:RC581-607 ,Histamine - Abstract
Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high-affinity receptor for IgE (FceR1), release histamine, inflammatory mediators, and cytokines following FceR1 cross-linking. Basophils are rare granulocytes in blood, lymphoid, and non-lymphoid tissues, and the difficulties to detect and isolate these cells has hampered the study of their biology and the understanding of their possible role in pathology. Furthermore, the existence of other FceR1-expressing cells, including professional Ag-presenting dendritic cells, generated some controversy regarding the ability of basophils to express MHC Class II molecules, present Ag and drive naive T cell differentiation into Th2 cells. The focus of this review is to present the recent advances on the interactions between basophils and peripheral blood and tissue memory Th1, Th2, and Th17 cells, as well as their potential role in IgE-independent non-allergic chronic inflammatory disorders, including human inflammatory bowel diseases. Basophils interactions with the innate players of IgE-dependent allergic inflammation, particularly innate lymphoid cells, will also be considered. The previously unrecognized function for basophils in skewing adaptive immune responses opens novel perspectives for the understanding of their contribution to the pathogenesis of inflammatory diseases.
- Published
- 2015
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