Increased Circulating and Urinary Levels of Soluble TAM Receptors in Diabetic Nephropathy
TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl...
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| Vydáno v: | The American journal of pathology Ročník 187; číslo 9; s. 1971 |
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| Hlavní autoři: | , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
01.09.2017
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| ISSN: | 1525-2191, 1525-2191 |
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| Abstract | TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl, and sMer were determined in 126 patients with diabetes assigned to a normoalbuminuric or macroalbuminuric (urinary albumin excretion <30 mg/24 hours and >300 mg/24 hours, respectively) study group and 18 healthy volunteers. TAM and protein S immunostaining was performed on kidney biopsy specimens from patients with diabetic nephropathy (n = 9) and controls (n = 6). TAM expression and shedding by tubular epithelial cells were investigated by PCR and enzyme-linked immunosorbent assay in an in vitro diabetes model. Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary sTyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue and glomerular depositions of protein S. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. Renal injury in diabetes is associated with elevated systemic and urine levels of sMer and sTyro3. This is the first study reporting excretion of sTAM receptors in urine, identifying the kidney as a source of sTAM. |
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| AbstractList | TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl, and sMer were determined in 126 patients with diabetes assigned to a normoalbuminuric or macroalbuminuric (urinary albumin excretion <30 mg/24 hours and >300 mg/24 hours, respectively) study group and 18 healthy volunteers. TAM and protein S immunostaining was performed on kidney biopsy specimens from patients with diabetic nephropathy (n = 9) and controls (n = 6). TAM expression and shedding by tubular epithelial cells were investigated by PCR and enzyme-linked immunosorbent assay in an in vitro diabetes model. Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary sTyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue and glomerular depositions of protein S. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. Renal injury in diabetes is associated with elevated systemic and urine levels of sMer and sTyro3. This is the first study reporting excretion of sTAM receptors in urine, identifying the kidney as a source of sTAM.TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl, and sMer were determined in 126 patients with diabetes assigned to a normoalbuminuric or macroalbuminuric (urinary albumin excretion <30 mg/24 hours and >300 mg/24 hours, respectively) study group and 18 healthy volunteers. TAM and protein S immunostaining was performed on kidney biopsy specimens from patients with diabetic nephropathy (n = 9) and controls (n = 6). TAM expression and shedding by tubular epithelial cells were investigated by PCR and enzyme-linked immunosorbent assay in an in vitro diabetes model. Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary sTyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue and glomerular depositions of protein S. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. Renal injury in diabetes is associated with elevated systemic and urine levels of sMer and sTyro3. This is the first study reporting excretion of sTAM receptors in urine, identifying the kidney as a source of sTAM. TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl, and sMer were determined in 126 patients with diabetes assigned to a normoalbuminuric or macroalbuminuric (urinary albumin excretion <30 mg/24 hours and >300 mg/24 hours, respectively) study group and 18 healthy volunteers. TAM and protein S immunostaining was performed on kidney biopsy specimens from patients with diabetic nephropathy (n = 9) and controls (n = 6). TAM expression and shedding by tubular epithelial cells were investigated by PCR and enzyme-linked immunosorbent assay in an in vitro diabetes model. Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary sTyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue and glomerular depositions of protein S. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. Renal injury in diabetes is associated with elevated systemic and urine levels of sMer and sTyro3. This is the first study reporting excretion of sTAM receptors in urine, identifying the kidney as a source of sTAM. |
| Author | Leemans, Jaklien C Claessen, Nike Roelofs, Joris J T H Lattenist, Lionel Uil, Melissa Florquin, Sandrine Kers, Jesper Gerdes, Victor E A Ochodnicky, Peter Meijers, Joost C M Ahdi, Mohamed |
| Author_xml | – sequence: 1 givenname: Peter surname: Ochodnicky fullname: Ochodnicky, Peter organization: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands – sequence: 2 givenname: Lionel surname: Lattenist fullname: Lattenist, Lionel organization: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands – sequence: 3 givenname: Mohamed surname: Ahdi fullname: Ahdi, Mohamed organization: Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands – sequence: 4 givenname: Jesper surname: Kers fullname: Kers, Jesper organization: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands – sequence: 5 givenname: Melissa surname: Uil fullname: Uil, Melissa organization: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands – sequence: 6 givenname: Nike surname: Claessen fullname: Claessen, Nike organization: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands – sequence: 7 givenname: Jaklien C surname: Leemans fullname: Leemans, Jaklien C organization: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands – sequence: 8 givenname: Sandrine surname: Florquin fullname: Florquin, Sandrine organization: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands – sequence: 9 givenname: Joost C M surname: Meijers fullname: Meijers, Joost C M organization: Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands – sequence: 10 givenname: Victor E A surname: Gerdes fullname: Gerdes, Victor E A organization: Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands; Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands – sequence: 11 givenname: Joris J T H surname: Roelofs fullname: Roelofs, Joris J T H email: j.j.roelofs@amc.nl organization: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: j.j.roelofs@amc.nl |
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| Snippet | TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to... |
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| SubjectTerms | Adult Aged Aged, 80 and over c-Mer Tyrosine Kinase Cell Line Diabetic Nephropathies - blood Diabetic Nephropathies - metabolism Diabetic Nephropathies - urine Female Humans Kidney Glomerulus - metabolism Male Middle Aged Protein S - metabolism Protein S - urine Proto-Oncogene Proteins - blood Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins - urine Receptor Protein-Tyrosine Kinases - blood Receptor Protein-Tyrosine Kinases - metabolism Receptor Protein-Tyrosine Kinases - urine |
| Title | Increased Circulating and Urinary Levels of Soluble TAM Receptors in Diabetic Nephropathy |
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