Dermal tissue fibrosis in patients with chronic venous insufficiency is associated with increased transforming growth factor-β1 gene expression and protein production

Abstract

Our study indicated that activated leukocytes traverse perivascular cuffs and release active TGF-beta(1). Positive TGF-beta(1) staining results of dermal fibroblasts were observed and suggest that fibroblasts are the targets of activated interstitial leukocytes. Increased protein production, despite normal levels of gene transcripts in patients in classes 5 and 6, suggests that alternate mechanisms other than gene transcription regulate protein production. A potential mechanism for quick access and release is storage of TGF-beta(1) in the extracellular matrix. IMG labeling to collagen fibrils support this possibility. Furthermore, TGF-beta(1) was exclusively elevated in areas of clinically active disease, indicating a regionalized response to injury. These data suggest that alterations in tissue remodeling occur in patients with CVI and that dermal tissue fibrosis in CVI is regulated by TGF-beta(1).

Pressure-induced cellular senescence: A mechanism linking venous hypertension to venous ulcers1

“…To test the hypothesis that elevated pressure produces premature senescence in dermal fibroblasts, we have developed an in vitro model using a special pressurized incubator [9] and a methodology to specifically test for cellular senescence. In addition, because TGF-␤ has been implicated as a possible mediator of inflammation and delayed healing of venous ulcers [10,11], we examined the effects of both pressure and TGF-␤ on cellular senescence, hypothesizing that TGF-␤ would accelerate the aging phenomenon.…”

Inhibition of mast cells by interleukin‐10 gene transfer contributes to protection against acute myocarditis in rats

“…1002/eji.200425147] suggested that there may be a link between increased mast cell density and endomyocardial fibrosis. Recent reports have demonstrated a definite role of mast cells in other fibrogenic disorders [19][20][21]. Paolocci et al [22] showed that the degranulation of mast cells and eosinophils might induce myocardial damage and dysfunction in rats challenged with Trichinella spiralis.…”

Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis

“…52,57,58 In BM fibrosis, activated monocytes are one of the cellular sources of TGF-␤. 6 Preliminary evidence indicated that the monocytes could be a source of the increased SP in the BM and circulation (unpublished observations).…”