TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain
TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain. Transforming growth factor-β (TGF-β) is a causal factor in experimental glomerulosclerosis, and it mediates the increased extracellular matrix (ECM) accumulation that occurs in cultured...
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| Veröffentlicht in: | Kidney international 1999-08, Vol.56 (2), p.428-439 |
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| creator | Riser, Bruce L. Ladson-Wofford, Stephanie Sharba, Abdulkarim Cortes, Pedro Drake, Katie Guerin, Christopher J. Yee, Jerry Choi, Mary E. Segarini, Patricia R. Narins, Robert G. |
| description | TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain.
Transforming growth factor-β (TGF-β) is a causal factor in experimental glomerulosclerosis, and it mediates the increased extracellular matrix (ECM) accumulation that occurs in cultured mesangial cells (MCs) exposed to high glucose concentrations and cyclic mechanical strain. This change is associated with increased levels of TGF-β, but may also involve alterations in receptor expression and binding.
Rat MCs cultured in media containing either 8 or 35 mM glucose were seeded into culture plates with elastin-coated flexible bottoms. Thereafter, they were subjected to cyclic stretch or static conditions and then examined for125I-TGF-β1 binding and expression of TGF-β receptors at the gene and protein levels.
Kinetic studies showed that MCs bound TGF-β1 in a time- and concentration-dependent manner, expressing 6800 high-affinity receptors per cell, with an apparent dissociation constant (Kd) of 15.4 pM, while cross-linking analysis identified three TGF-β receptors (βR) corresponding to βRI, βRII, and βRIII of 54, 73, and 200 kDa, respectively. Immunocytochemical studies of βRI and βRII protein revealed MC expression in a homogeneous, punctate distribution, whereas Northern analysis demonstrated the presence of the corresponding mRNAs. Exposure to cyclic stretching significantly increased (10%) the overall number of TGF-β receptors, whereas ligands associated with βRs I, II, and III also increased (25 to 50%). The finding of increased (30 to 40%) βRI and βRII transcript levels and immunoreactive protein (163 and 59%, respectively) in the absence of significant changes in the apparent Kd indicated that stretch-induced binding was the result of increased receptor synthesis and expression and not due to a change in binding affinity. In a similar, but more dramatic fashion, exposure to high glucose also elevated (50%) the receptor number, as well as the amount of ligands associated with βRs I, II, and III (100 to 250%). This same treatment also increased the levels of βRI and βRII mRNA (30 to 40%) and the immunoreactive protein (82 and 82%, respectively), without significantly altering the binding affinity of the receptor. A concerted or synergistic effect of both stimuli was not evidenced.
These results suggest that the modulation of TGF-β receptors may be an additional control point in mediating the glucose- and mechanical force-induced increase in EC |
| doi_str_mv | 10.1046/j.1523-1755.1999.00600.x |
| format | Article |
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Transforming growth factor-β (TGF-β) is a causal factor in experimental glomerulosclerosis, and it mediates the increased extracellular matrix (ECM) accumulation that occurs in cultured mesangial cells (MCs) exposed to high glucose concentrations and cyclic mechanical strain. This change is associated with increased levels of TGF-β, but may also involve alterations in receptor expression and binding.
Rat MCs cultured in media containing either 8 or 35 mM glucose were seeded into culture plates with elastin-coated flexible bottoms. Thereafter, they were subjected to cyclic stretch or static conditions and then examined for125I-TGF-β1 binding and expression of TGF-β receptors at the gene and protein levels.
Kinetic studies showed that MCs bound TGF-β1 in a time- and concentration-dependent manner, expressing 6800 high-affinity receptors per cell, with an apparent dissociation constant (Kd) of 15.4 pM, while cross-linking analysis identified three TGF-β receptors (βR) corresponding to βRI, βRII, and βRIII of 54, 73, and 200 kDa, respectively. Immunocytochemical studies of βRI and βRII protein revealed MC expression in a homogeneous, punctate distribution, whereas Northern analysis demonstrated the presence of the corresponding mRNAs. Exposure to cyclic stretching significantly increased (10%) the overall number of TGF-β receptors, whereas ligands associated with βRs I, II, and III also increased (25 to 50%). The finding of increased (30 to 40%) βRI and βRII transcript levels and immunoreactive protein (163 and 59%, respectively) in the absence of significant changes in the apparent Kd indicated that stretch-induced binding was the result of increased receptor synthesis and expression and not due to a change in binding affinity. In a similar, but more dramatic fashion, exposure to high glucose also elevated (50%) the receptor number, as well as the amount of ligands associated with βRs I, II, and III (100 to 250%). This same treatment also increased the levels of βRI and βRII mRNA (30 to 40%) and the immunoreactive protein (82 and 82%, respectively), without significantly altering the binding affinity of the receptor. A concerted or synergistic effect of both stimuli was not evidenced.
These results suggest that the modulation of TGF-β receptors may be an additional control point in mediating the glucose- and mechanical force-induced increase in ECM deposition by MCs.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1046/j.1523-1755.1999.00600.x</identifier><identifier>PMID: 10432381</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Activin Receptors, Type I ; Adrenals. Adrenal axis. Renin-angiotensin system (diseases) ; Animals ; Biological and medical sciences ; Blotting, Northern ; cell elasticity ; Cells, Cultured ; Cross-Linking Reagents - metabolism ; Diabetes Mellitus, Experimental - metabolism ; diabetic kidney disease ; Dose-Response Relationship, Drug ; Elasticity ; Endocrinopathies ; extracellular matrix ; Extracellular Matrix - metabolism ; fibrosis ; Fluorescent Antibody Technique ; Gene Expression - drug effects ; Gene Expression - physiology ; Glomerular Mesangium - chemistry ; Glomerular Mesangium - cytology ; Glomerular Mesangium - metabolism ; glomerulosclerosis ; Glucose - pharmacology ; Iodine Radioisotopes ; Kinetics ; Malignant tumors ; Medical sciences ; Protein Binding - drug effects ; Protein-Serine-Threonine Kinases - analysis ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Rats ; Rats, Inbred F344 ; Receptors, Transforming Growth Factor beta - analysis ; Receptors, Transforming Growth Factor beta - genetics ; Receptors, Transforming Growth Factor beta - metabolism ; RNA, Messenger - analysis ; scarring ; Space life sciences ; Stress, Mechanical ; tissue repair ; transforming growth factor-β</subject><ispartof>Kidney international, 1999-08, Vol.56 (2), p.428-439</ispartof><rights>1999 International Society of Nephrology</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-50b8758592020ebaf4f1aa955577501f4432ddb131776d3d180c10e52279dcf53</citedby><cites>FETCH-LOGICAL-c449t-50b8758592020ebaf4f1aa955577501f4432ddb131776d3d180c10e52279dcf53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1920623$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10432381$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Riser, Bruce L.</creatorcontrib><creatorcontrib>Ladson-Wofford, Stephanie</creatorcontrib><creatorcontrib>Sharba, Abdulkarim</creatorcontrib><creatorcontrib>Cortes, Pedro</creatorcontrib><creatorcontrib>Drake, Katie</creatorcontrib><creatorcontrib>Guerin, Christopher J.</creatorcontrib><creatorcontrib>Yee, Jerry</creatorcontrib><creatorcontrib>Choi, Mary E.</creatorcontrib><creatorcontrib>Segarini, Patricia R.</creatorcontrib><creatorcontrib>Narins, Robert G.</creatorcontrib><title>TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain.
Transforming growth factor-β (TGF-β) is a causal factor in experimental glomerulosclerosis, and it mediates the increased extracellular matrix (ECM) accumulation that occurs in cultured mesangial cells (MCs) exposed to high glucose concentrations and cyclic mechanical strain. This change is associated with increased levels of TGF-β, but may also involve alterations in receptor expression and binding.
Rat MCs cultured in media containing either 8 or 35 mM glucose were seeded into culture plates with elastin-coated flexible bottoms. Thereafter, they were subjected to cyclic stretch or static conditions and then examined for125I-TGF-β1 binding and expression of TGF-β receptors at the gene and protein levels.
Kinetic studies showed that MCs bound TGF-β1 in a time- and concentration-dependent manner, expressing 6800 high-affinity receptors per cell, with an apparent dissociation constant (Kd) of 15.4 pM, while cross-linking analysis identified three TGF-β receptors (βR) corresponding to βRI, βRII, and βRIII of 54, 73, and 200 kDa, respectively. Immunocytochemical studies of βRI and βRII protein revealed MC expression in a homogeneous, punctate distribution, whereas Northern analysis demonstrated the presence of the corresponding mRNAs. Exposure to cyclic stretching significantly increased (10%) the overall number of TGF-β receptors, whereas ligands associated with βRs I, II, and III also increased (25 to 50%). The finding of increased (30 to 40%) βRI and βRII transcript levels and immunoreactive protein (163 and 59%, respectively) in the absence of significant changes in the apparent Kd indicated that stretch-induced binding was the result of increased receptor synthesis and expression and not due to a change in binding affinity. In a similar, but more dramatic fashion, exposure to high glucose also elevated (50%) the receptor number, as well as the amount of ligands associated with βRs I, II, and III (100 to 250%). This same treatment also increased the levels of βRI and βRII mRNA (30 to 40%) and the immunoreactive protein (82 and 82%, respectively), without significantly altering the binding affinity of the receptor. A concerted or synergistic effect of both stimuli was not evidenced.
These results suggest that the modulation of TGF-β receptors may be an additional control point in mediating the glucose- and mechanical force-induced increase in ECM deposition by MCs.</description><subject>Activin Receptors, Type I</subject><subject>Adrenals. Adrenal axis. Renin-angiotensin system (diseases)</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>cell elasticity</subject><subject>Cells, Cultured</subject><subject>Cross-Linking Reagents - metabolism</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>diabetic kidney disease</subject><subject>Dose-Response Relationship, Drug</subject><subject>Elasticity</subject><subject>Endocrinopathies</subject><subject>extracellular matrix</subject><subject>Extracellular Matrix - metabolism</subject><subject>fibrosis</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression - physiology</subject><subject>Glomerular Mesangium - chemistry</subject><subject>Glomerular Mesangium - cytology</subject><subject>Glomerular Mesangium - metabolism</subject><subject>glomerulosclerosis</subject><subject>Glucose - pharmacology</subject><subject>Iodine Radioisotopes</subject><subject>Kinetics</subject><subject>Malignant tumors</subject><subject>Medical sciences</subject><subject>Protein Binding - drug effects</subject><subject>Protein-Serine-Threonine Kinases - analysis</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Receptors, Transforming Growth Factor beta - analysis</subject><subject>Receptors, Transforming Growth Factor beta - genetics</subject><subject>Receptors, Transforming Growth Factor beta - metabolism</subject><subject>RNA, Messenger - analysis</subject><subject>scarring</subject><subject>Space life sciences</subject><subject>Stress, Mechanical</subject><subject>tissue repair</subject><subject>transforming growth factor-β</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFO3DAQhq2qVdnSvgLyAfWW1I7jJObWIqCVqLjA2XLsyeJV1lk8Cdp9LR6kz1SHXQE3Tpbl7x_PfEMI5SznrKx-rHIuC5HxWsqcK6VyxirG8u0Hsnh5-EgWjDUyK6RojsgXxBVLdyXYZ3KUiohCNHxBHm6vLrN_TzSChc04RArbTQREPwRqgqOtD86HJfWBRjPSNaAJS296aqHv8Yz-HdzUm3HG2x1d9pMdEJ6Tdmd7b1PC3pvgbYrgGI0PX8mnzvQI3w7nMbm7vLg9_51d31z9Of95ndmyVGMmWdvUspGqYAWD1nRlx41RUsq6lox3ZZrAuZYLXteVE443zHIGsihq5WwnxTH5vq-7icPDBDjqtce5axNgmFBXSpVlrcoENnvQxgExQqc30a9N3GnO9Kxbr_RsVc9W9axbP-vW2xQ9OfwxtWtwb4J7vwk4PQAGk4IummA9vnJpuqoQCfu1xyAJefQQNVoPwYLzaTGjdoN_v5n_772e0A</recordid><startdate>19990801</startdate><enddate>19990801</enddate><creator>Riser, Bruce L.</creator><creator>Ladson-Wofford, Stephanie</creator><creator>Sharba, Abdulkarim</creator><creator>Cortes, Pedro</creator><creator>Drake, Katie</creator><creator>Guerin, Christopher J.</creator><creator>Yee, Jerry</creator><creator>Choi, Mary E.</creator><creator>Segarini, Patricia R.</creator><creator>Narins, Robert G.</creator><general>Elsevier Inc</general><general>Nature Publishing</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19990801</creationdate><title>TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain</title><author>Riser, Bruce L. ; Ladson-Wofford, Stephanie ; Sharba, Abdulkarim ; Cortes, Pedro ; Drake, Katie ; Guerin, Christopher J. ; Yee, Jerry ; Choi, Mary E. ; Segarini, Patricia R. ; Narins, Robert G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-50b8758592020ebaf4f1aa955577501f4432ddb131776d3d180c10e52279dcf53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Activin Receptors, Type I</topic><topic>Adrenals. Adrenal axis. Renin-angiotensin system (diseases)</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>cell elasticity</topic><topic>Cells, Cultured</topic><topic>Cross-Linking Reagents - metabolism</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>diabetic kidney disease</topic><topic>Dose-Response Relationship, Drug</topic><topic>Elasticity</topic><topic>Endocrinopathies</topic><topic>extracellular matrix</topic><topic>Extracellular Matrix - metabolism</topic><topic>fibrosis</topic><topic>Fluorescent Antibody Technique</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression - physiology</topic><topic>Glomerular Mesangium - chemistry</topic><topic>Glomerular Mesangium - cytology</topic><topic>Glomerular Mesangium - metabolism</topic><topic>glomerulosclerosis</topic><topic>Glucose - pharmacology</topic><topic>Iodine Radioisotopes</topic><topic>Kinetics</topic><topic>Malignant tumors</topic><topic>Medical sciences</topic><topic>Protein Binding - drug effects</topic><topic>Protein-Serine-Threonine Kinases - analysis</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Receptors, Transforming Growth Factor beta - analysis</topic><topic>Receptors, Transforming Growth Factor beta - genetics</topic><topic>Receptors, Transforming Growth Factor beta - metabolism</topic><topic>RNA, Messenger - analysis</topic><topic>scarring</topic><topic>Space life sciences</topic><topic>Stress, Mechanical</topic><topic>tissue repair</topic><topic>transforming growth factor-β</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Riser, Bruce L.</creatorcontrib><creatorcontrib>Ladson-Wofford, Stephanie</creatorcontrib><creatorcontrib>Sharba, Abdulkarim</creatorcontrib><creatorcontrib>Cortes, Pedro</creatorcontrib><creatorcontrib>Drake, Katie</creatorcontrib><creatorcontrib>Guerin, Christopher J.</creatorcontrib><creatorcontrib>Yee, Jerry</creatorcontrib><creatorcontrib>Choi, Mary E.</creatorcontrib><creatorcontrib>Segarini, Patricia R.</creatorcontrib><creatorcontrib>Narins, Robert G.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Kidney international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Riser, Bruce L.</au><au>Ladson-Wofford, Stephanie</au><au>Sharba, Abdulkarim</au><au>Cortes, Pedro</au><au>Drake, Katie</au><au>Guerin, Christopher J.</au><au>Yee, Jerry</au><au>Choi, Mary E.</au><au>Segarini, Patricia R.</au><au>Narins, Robert G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain</atitle><jtitle>Kidney international</jtitle><addtitle>Kidney Int</addtitle><date>1999-08-01</date><risdate>1999</risdate><volume>56</volume><issue>2</issue><spage>428</spage><epage>439</epage><pages>428-439</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain.
Transforming growth factor-β (TGF-β) is a causal factor in experimental glomerulosclerosis, and it mediates the increased extracellular matrix (ECM) accumulation that occurs in cultured mesangial cells (MCs) exposed to high glucose concentrations and cyclic mechanical strain. This change is associated with increased levels of TGF-β, but may also involve alterations in receptor expression and binding.
Rat MCs cultured in media containing either 8 or 35 mM glucose were seeded into culture plates with elastin-coated flexible bottoms. Thereafter, they were subjected to cyclic stretch or static conditions and then examined for125I-TGF-β1 binding and expression of TGF-β receptors at the gene and protein levels.
Kinetic studies showed that MCs bound TGF-β1 in a time- and concentration-dependent manner, expressing 6800 high-affinity receptors per cell, with an apparent dissociation constant (Kd) of 15.4 pM, while cross-linking analysis identified three TGF-β receptors (βR) corresponding to βRI, βRII, and βRIII of 54, 73, and 200 kDa, respectively. Immunocytochemical studies of βRI and βRII protein revealed MC expression in a homogeneous, punctate distribution, whereas Northern analysis demonstrated the presence of the corresponding mRNAs. Exposure to cyclic stretching significantly increased (10%) the overall number of TGF-β receptors, whereas ligands associated with βRs I, II, and III also increased (25 to 50%). The finding of increased (30 to 40%) βRI and βRII transcript levels and immunoreactive protein (163 and 59%, respectively) in the absence of significant changes in the apparent Kd indicated that stretch-induced binding was the result of increased receptor synthesis and expression and not due to a change in binding affinity. In a similar, but more dramatic fashion, exposure to high glucose also elevated (50%) the receptor number, as well as the amount of ligands associated with βRs I, II, and III (100 to 250%). This same treatment also increased the levels of βRI and βRII mRNA (30 to 40%) and the immunoreactive protein (82 and 82%, respectively), without significantly altering the binding affinity of the receptor. A concerted or synergistic effect of both stimuli was not evidenced.
These results suggest that the modulation of TGF-β receptors may be an additional control point in mediating the glucose- and mechanical force-induced increase in ECM deposition by MCs.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>10432381</pmid><doi>10.1046/j.1523-1755.1999.00600.x</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Activin Receptors, Type I Adrenals. Adrenal axis. Renin-angiotensin system (diseases) Animals Biological and medical sciences Blotting, Northern cell elasticity Cells, Cultured Cross-Linking Reagents - metabolism Diabetes Mellitus, Experimental - metabolism diabetic kidney disease Dose-Response Relationship, Drug Elasticity Endocrinopathies extracellular matrix Extracellular Matrix - metabolism fibrosis Fluorescent Antibody Technique Gene Expression - drug effects Gene Expression - physiology Glomerular Mesangium - chemistry Glomerular Mesangium - cytology Glomerular Mesangium - metabolism glomerulosclerosis Glucose - pharmacology Iodine Radioisotopes Kinetics Malignant tumors Medical sciences Protein Binding - drug effects Protein-Serine-Threonine Kinases - analysis Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Rats Rats, Inbred F344 Receptors, Transforming Growth Factor beta - analysis Receptors, Transforming Growth Factor beta - genetics Receptors, Transforming Growth Factor beta - metabolism RNA, Messenger - analysis scarring Space life sciences Stress, Mechanical tissue repair transforming growth factor-β |
| title | TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain |
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