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- Title
TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain.
- Authors
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.
- Abstract
TGF-β receptor expression and binding in rat mesangial cells: Modulation by glucose and cyclic mechanical strain. Background. 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. Methods. 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 for 125 I-TGF-β1 binding and expression of TGF-β receptors at the gene and protein levels. Results. 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...
- Subjects
TRANSFORMING growth factors-beta; EXTRACELLULAR matrix
- Publication
Kidney International, 1999, Vol 56, Issue 2, p428
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.1999.00600.x