title: Preferential secretion of collagen type 3 versus type 1 from adventitial fibroblasts stimulated by TGF-β/Smad3-treated medial smooth muscle cells.
abstract: Restenosis, or arterial lumen re-narrowing, occurs in 30-50% of the patients undergoing angioplasty. Adaptive remodeling is the compensatory enlargement of the vessel size, and has been reported to prevent the deleterious effects of restenosis. Our previous studies have shown that elevated transforming growth factor (TGF-β) and its signaling protein Smad3 in the media layer induce adaptive remodeling of angioplastied rat carotid artery accompanying an increase of total collagen in the adventitia. In order to gain insights into a possible role of collagen in Smad3-induced adaptive remodeling, here we have investigated a mechanism of cell-cell communication between medial smooth muscle cells (SMCs) and adventitial fibroblasts in regulating the secretion of two major collagen subtypes. We have identified a preferential collagen-3 versus collagen-1 secretion by adventitial fibroblasts following stimulation by the conditioned medium from the TGF-β1-treated/Smad3-expressing medial smooth muscle cells (SMCs), which contained higher levels of CTGF and IGF2 as compared to control medium. Treating the TGF-β/Smad3-stimulated SMCs with an siRNA to either CTGF or IGF2 reversed the effect of conditioned media on preferential collagen-3 secretion from fibroblasts. Moreover, recombinant CTGF and IGF2 together stimulated adventitial fibroblasts to preferentially secrete collagen-3 versus collagen-1. This is the first study to identify a preferential secretion of collagen-3 versus collagen-1 from adventitial fibroblasts as a result of TGF-β/Smad3 stimulation of medial SMCs, and that CTGF and IGF2 function together to mediate this signaling communication between the two cell types.
authors.affiliation: Department of Surgery, University of Wisconsin, 1111 Highland Ave, Madison, WI 53705, USA.
authors.forename: Shakti A
authors.initials: SA
authors.lastname: Goel
authors.forename: Lian-Wang
authors.initials: LW
authors.lastname: Guo
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Shi
authors.forename: Rishi
authors.initials: R
authors.lastname: Kundi
authors.forename: Gregory
authors.initials: G
authors.lastname: Sovinski
authors.forename: Stephen
authors.initials: S
authors.lastname: Seedial
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: K Craig
authors.initials: KC
authors.lastname: Kent
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D049452:Green Fluorescent Proteins; D007335:Insulin-Like Growth Factor II