Altered proliferative responses of dermal fibroblasts to TGF-beta1 may contribute to chronic venous stasis ulcer

Journal of Vascular Surgery
B K LalW N Durán

Abstract

Venous ulcer fibroblasts demonstrate decreased proliferative responses to growth factor stimulation, suggesting cellular senescence. However, the role of chronic venous insufficiency (CVI) disease progression and extracellular matrix (ECM) proteins in agonist-induced cellular proliferation is ill-defined. We hypothesize that CVI-induced fibroblast proliferative resistance to growth factors worsens with disease progression and is regulated by the composition of ECM. Fibroblast explants were isolated from biopsy specimens from two patients without CVI and 16 patients with CVI of the lower calf (LC) and lower thigh (LT) and stratified according to CEAP disease severity: non-CVI (NC; n = 2), class 2-3 (n = 5), class 4 (n = 5), class 5 (n = 3), and class 6 (n = 3). Proliferation experiments were standardized with a neonatal foreskin fibroblast cell line (HS68). A 10-day course and dose response experiment with 0, 0.5, 1.0, 2.5, 5, 10, and 20 ng/mL of transforming growth factor-beta(1) (TGF-beta(1)) demonstrated maximal cell proliferation at 5 ng/mL of TGF-beta(1) on day 4. Under these conditions, CVI dermal fibroblasts were challenged with and without TGF-beta(1) and evaluated for proliferative responses on plates coated with polyst...Continue Reading

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Citations

Jun 21, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Shubha VarmaWalter N Durán
Nov 16, 2013·BMC Medicine·Jonathan S AlexanderAlireza Minagar
May 28, 2013·Acta histochemica·Vinay KantDinesh Kumar
Aug 3, 2007·The Journal of Investigative Dermatology·Ganary DabiriLivingston Van de Water
Jun 1, 2005·The Nursing Clinics of North America·JoAnne D Whitney
Sep 25, 2007·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·L PascarellaG W Schmid-Schönbein
Dec 1, 2004·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·M S GohelM R Whyman
Jun 28, 2008·Vascular and Endovascular Surgery·Joseph D RaffettoJames O Menzoian
Dec 1, 2017·International Journal of Molecular Sciences·Pedro SerralheiroIgnacio Verde
Jan 14, 2011·Plastic and Reconstructive Surgery·Joseph D Raffetto, William A Marston
Jul 9, 2017·Scientific Reports·Yuriko TakeuchiKimikazu Hamano
Feb 3, 2021·Nano Convergence·Hafiz Muhammad Umer FarooqiKyung Hyun Choi
Dec 31, 2020·Journal of Clinical Medicine·Joseph D RaffettoFerdinando Mannello
Apr 16, 2021·The International Journal of Lower Extremity Wounds·Vinay KantDinesh Kumar
Jun 30, 2009·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·P J PappasW N Durán

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