Antagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis. Possible implications for dermal wound healing

1992 ◽  
Vol 102 (3) ◽  
pp. 447-456 ◽  
Author(s):  
I. Ellis ◽  
A.M. Grey ◽  
A.M. Schor ◽  
S.L. Schor

The migration of adult skin fibroblasts into three-dimensional collagen gel matrices is differentially affected by cell density, with subconfluent cells displaying a significantly elevated level of migration compared to confluent ones. Fetal fibroblasts differ from adult cells in that they display an elevated level of migration at both subconfluent and confluent cell densities. We have previously reported that this difference in behaviour results from the secretion by fetal fibroblasts of a ‘migration stimulating factor’ (MSF) which is not made by their normal adult counterparts, and that MSF appears to act by stimulating the synthesis of hyaluronic acid (HA). Data presented in this communication indicate that (a) MSF specifically stimulates the synthesis of high molecular weight species of HA, (b) TGF-beta 1 inhibits the elevated migration of adult fibroblasts plated at subconfluent cell density, (c) under these conditions, TGF-beta 1 induces a parallel decrease in the synthesis of high molecular weight HA and increase in the synthesis of low molecular weight HA, (d) TGF-beta 1 is a potent antagonist of MSF, effectively blocking its stimulation of cell migration and synthesis of high molecular weight HA, and (e) the inhibition of fibroblast migration by TGF-beta 1 does not appear to be a chemotactic response dependent upon the existence of a concentration gradient of the cytokine. Our observations regarding the inhibitory effects of TGF-beta 1 on fibroblast migration into 3D collagen gels stand in marked contrast to various published reports indicating that this cytokine stimulates the migration of human skin fibroblasts through the pores of polycarbonate filters as used in modified Boyden chamber assays; this discrepancy underscores the importance of the substratum in modulating cellular response to cytokines. Our results are discussed in terms of the possible combined contribution of MSF and TGF-beta 1 to wound healing.

1992 ◽  
Vol 57 (10) ◽  
pp. 2151-2156 ◽  
Author(s):  
Peter Chabreček ◽  
Ladislav Šoltés ◽  
Hynek Hradec ◽  
Jiří Filip ◽  
Eduard Orviský

Two methods for the preparation of high molecular weight [3H]hyaluronic acid were investigated. In the first one, hydrogen atoms in the molecule were replaced by tritium. This isotopic substitution was performed in aqueous solution using Pd/CaCO3 as the catalyst. In the second method, the high molecular weight hyaluronic acid was alkylated with [3H]methyl bromide in liquid ammonia at a temperature of -33.5 °C. High-performance gel permeation chromatographic separation method was used for the isolation and characterization of the high molecular weight [3H]hyaluronic acid. Molecular weight parameters for the labelled biopolymers were Mw = 128 kDa, Mw/Mn = 1.88 (first method) and Mw = 268 kDa, Mw/Mn = 1.55 (second method). The high molecular weight [3H]hyaluronic acid having Mw = 268 kDa was degraded further by specific hyaluronidase. Products of the enzymatic depolymerization were observed to be identical for both, labelled and cold biopolymer. This finding indicates that the described labelling procedure using [3H]methyl bromide does not induce any major structural rearrangements in the molecule.


2021 ◽  
Vol 14 (4) ◽  
pp. 301
Author(s):  
Yayoi Kawano ◽  
Viorica Patrulea ◽  
Emmanuelle Sublet ◽  
Gerrit Borchard ◽  
Takuya Iyoda ◽  
...  

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.


Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2434-2437
Author(s):  
SR Newcom ◽  
LH Muth ◽  
ET Parker

High molecular weight transforming growth factor-beta (TGF beta) is a physiologically active TGF secreted by nodular sclerosing Reed- Sternberg cells. Five monoclonal murine antibodies were prepared that distinguished Hodgkin's TGF beta from platelet-derived TGF beta using an enzyme-linked immunosorbent assay, neutralization of biologic activity, and Western blotting. These monoclonal antibodies directed at unique antigenic determinants (epitopes) of Hodgkin's TGF beta will allow further characterization of the role of Hodgkin's TGF beta in Hodgkin's disease and related entities.


2015 ◽  
Vol 642 ◽  
pp. 94-98
Author(s):  
Chau Chang Chou ◽  
Yu Hsiang Hao ◽  
Fu Yin Hsu

The surface of high-pressure crystallized ultra-high molecular weight polyethylene (UHMWPE) was modified for application as an artificial cartilage material. A UHMWPE surface pretreated by a series of processes, including treatment with O2-plasma and ethylenediamine solution, was coated with hyaluronic acid (HA). After that, adipic acid dihydrazide (AAD) was added to partially crosslink the HA coating in order to enhance its durability. The modified samples were verified by water contact angle measurement and Fourier transform infrared spectrometry. Both HA layers, original and crosslinked, were also quantitatively evaluated by carbohydrate chemistry assay according to the absorbance of the incident light. The tribological performance of the samples was evaluated by a pin-on-disk test rig lubricated by normal saline under an average pressure of 18 MPa and at a sliding speed of 0.03 m/s for 45 h. The wear resistance of the HA-coated UHMWPE specimens promoted by the crosslink process was superior to that of the original HA-coated sample, and that resistance was maintained after immersion in saline solution for one month.


2018 ◽  
Vol 159 (36) ◽  
pp. 1475-1482 ◽  
Author(s):  
Szonja Vingender ◽  
László Restár ◽  
Krisztián Benedek Csomó ◽  
Péter Schmidt ◽  
Péter Hermann ◽  
...  

Abstract: Introduction: Derangement of the temporomandibular joint complicates everyday life, due to the masticatory malfunction and the continuous pain sensation of the head and facial region. The therapy is multidisciplinary and varying. In case of the inefficiency of conservative therapy, minimally invasive intervention is needed with intraarticular injection. Aim: The aim of our study was to examine whether hyaluronic acid injection is more beneficial compared to corticosteroid in 37 joints. We also examined whether the efficacy of the therapy is influenced by hyaluronic acid molecular weight and the used protocol. Method: Wilkes stage, maximal mouth opening and the Visual Analogue Scale were determined pre-operatively and 6 months later. Corticosteroid application was performed once, hyaluronic acid was injected on a weekly bases 3 times in a row, by use of low (6–10 × 105 dalton) or high molecular weight (24–36 × 105 dalton) preparations. Results: The medical state of the patients treated with corticosteroid temporarily improved, but the symptoms returned. Due to hyaluronic acid treatment, significant improvement was revealed in all parameters (pwilkes<0.0001; pmouth-opening = 0.0002; pVAS<0.0001). There was no significant relapse (T = 2.05). The third administration of hyaluronic acid resulted in a significant improvement of the Visual Analogue Scale compared to the first and second injection (T3.–1. = 20.37; T3.–2. = 9.57). Conclusions: Comparing the two agents we can state that hyaluronic acid was significantly more effective and its application for three times seems to be the most effective treatment decreasing the symptoms. The high molecular weight solution was more effective in increasing mouth opening. In contrast to hyaluronic acid, corticosteroid had no prolonged effect in higher Wilkes stages. Orv Hetil. 2018; 159(36): 1475–1482.


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