Altered proliferative responses of dermal fibroblasts to TGF-β1 may contribute to chronic venous stasis ulcer

Abstract

These data indicate that clinical disease progression correlates with cellular dysfunction. Fibroblasts from patients with class 2-3 disease retain their unstimulated and agonist- induced proliferative capacity, compared with NC and HS68 cells. The onset of inflammatory skin changes (class 4 and class 5 disease) diminishes agonist-induced proliferation, and ulcer formation (class 6 disease) severely inhibits it. In addition, the composition of ECM does not affect TGF-beta(1)-induced proliferation of fibroblasts in CVI.

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

“…On the other hand, the absence of an effect may have been due to the dose of TGF-␤ (1 ng/ml) used in this study. Lal et al recently performed a dose-response experiment with TGF-␤ on cultured fibroblasts and found a maximal response with a higher dose (5 ng/ml) [12]. On the other hand, their incubation period was much shorter (4 days) compared to the present investigation (20 and 27 days).…”

“…Gene expression for TGF-␤ was only elevated in the patients with the least severe disease (CEAP class 4), suggesting that early in the course of the disease, TGF-␤ expression is a normal response to healing which disappears after prolonged, significant fibrosis develops [11]. These findings, suggesting TGF-␤ was a mediator in the development of ulceration in CVI, were confirmed in a subsequent study [12].…”

Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats

“…5A). TGF-b also has a chemoattractant effect on fibroblasts and stimulates their proliferation [57]. Thus, in present study, increased expression of TGF-b 1 in SP-treated wound was responsible for the marked proliferation of fibroblasts, which in turn cause more collagen deposition.…”

Management of venous leg ulcers: Clinical practice guidelines of the Society for Vascular Surgery® and the American Venous Forum

“…Although a significant body of research has identified that VLUs are associated with significant upregulation of inflammatory cytokines and proteases, 71,83,253 there is a lack of data identifying that any anti-inflammatory dressing other than compression is associated with accelerated healing of VLUs. 254 …”