scholarly journals Genistein does not Inhibit TGF-β1-Induced Conversion of Human Dermal Fibroblasts to Myofibroblasts

2021 ◽  
pp. 815-820
Author(s):  
M KAŇUCHOVÁ ◽  
L URBAN ◽  
N MELEGOVÁ ◽  
M ČOMA ◽  
B DVOŘÁNKOVÁ ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Dermal Fibroblasts ◽  
Point Of View ◽  
Human Dermal Fibroblasts ◽  
Receptor Modulator ◽  
Naturally Occurring ◽  
Growth Factor Beta ◽  
Tgf Β1

Transforming growth factor beta 1 (TGF-β1) is a pro-fibrotic cytokine with a key role in wound repair and regeneration, including induction of fibroblast-to-myofibroblast transition. Genistein is a naturally occurring selective estrogen receptor modulator with promising anti-fibrotic properties. In the present study we aimed to investigate whether genistein modulates TGF-β1 (canonical and non-canonical) signaling in normal dermal fibroblasts at the protein level (Western blot and immunofluo-rescence). We demonstrated that TGF-β1 induces the myofibroblast-like phenotype in the studied fibroblast signaling via canonical (SMAD) and non-canonical (AKT, ERK1/2, ROCK) pathways. Genistein induced only ERK1/2 expression, whereas the combination of TGF-β1 and genistein attenuated the ERK1/2 and ROCK signaling. Of note, the other studied pathways remained almost unaffected. From this point of view, genistein does not impair conversion of normal fibroblasts to myofibroblast-like cells.

Effect of a Porous Suture Containing Transforming Growth Factor Beta 1 on Healing After Rotator Cuff Repair in a Rat Model

2021 ◽  
pp. 036354652110285
Author(s):  
Jong Pil Yoon ◽  
Hun-Min Kim ◽  
Jin-Hyun Choi ◽  
Hae Rim Kang ◽  
Dong Hyun Kim ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Rat Model ◽  
Transforming Growth Factor Beta ◽  
Rotator Cuff Repair ◽  
Animal Experiment ◽  
Transforming Growth Factor ◽  
Group 3 ◽  
Growth Factor Beta ◽  
Cuff Repair ◽  
Tgf Β1

Background: The healing failure rate after rotator cuff repair is considerably high. Purpose: To evaluate the effect of a porous suture containing transforming growth factor beta 1 (TGF-β1) on the sustained release of TGF-β1 and rotator cuff healing in a rat model. Study Design: Controlled laboratory study. Methods: A porous suture was developed, and its tensile strength was measured. TGF-β1 was delivered using the porous suture, and a TGF-β1 release test and human fibroblast proliferation assay were performed. For the animal experiment, 30 rats were randomly allocated into 3 groups (n = 10 each). A bilateral supraspinatus tendon tear was made in all the rats, and repair was performed. Group 1 received repair only; group 2, repair and a single injection of TGF-β1; and group 3, repair using the porous suture containing TGF-β1. Eight weeks after repair, biomechanical and histological analyses were performed. Results: The porous suture was successfully developed with mechanical properties compatible with the conventional suture, and the sustained release of TGF-β1 from the porous suture was confirmed. In addition, the cell proliferation assay confirmed the biological safety of the porous suture. In the animal experiment, group 3 biomechanically exhibited the largest cross-sectional area and the highest ultimate failure load and ultimate stress (all P < .05). Histological examination revealed that group 3 showed significantly better collagen fiber density and tendon-to-bone maturation than did groups 1 and 2 (all P < .05). Conclusion: The porous suture containing TGF-β1 could sustainedly and safely release TGF-β1, and its use during rotator cuff repair could improve rotator cuff healing, as assessed on the basis of the biomechanical and histological changes in the rat model in this study. Considering the effectiveness, safety, and convenience of the porous suture without extra effort in surgery, the findings of the present study will have a far-reaching effect on the treatment of rotator cuff tears. Clinical Relevance: The porous suture containing TGF-β1 might improve healing after rotator cuff repair.

Attenuation of diethyl nitrosamine-induced hepatocellular carcinoma by taxifolin and/or alogliptin: The interplay between toll-like receptor 4, transforming growth factor beta-1, and apoptosis

2021 ◽  
pp. 096032712110084
Author(s):  
AM Kabel ◽  
HH Arab ◽  
MA Abd Elmaaboud
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transforming Growth Factor Beta ◽  
Caspase 3 ◽  
Transforming Growth Factor ◽  
Liver Function Tests ◽  
Toll Like Receptor ◽  
Caspase 9 ◽  
Toll Like Receptor 4 ◽  
Growth Factor Beta ◽  
Tgf Β1

Hepatocellular carcinoma (HCC) is the most common form of liver malignancies worldwide. Alogliptin is an anti-diabetic that may have effective anticancer properties against many types of malignancies. Taxifolin is a flavonoid that has potent antioxidant, and anti-inflammatory properties. The objective of this study was to explore the impact of alogliptin and/or taxifolin on diethyl nitrosamine-induced HCC in rats. One hundred male Wistar rats were divided into five equal groups as follows: Control; HCC; HCC + Alogliptin; HCC + Taxifolin; and HCC + Alogliptin + Taxifolin group. The survival rate, liver function tests, tissue antioxidant enzymes, malondialdehyde (MDA), nuclear factor (erythroid derived 2)-like 2 (Nrf2), transforming growth factor beta 1 (TGF-β1), interleukin 1 alpha (IL-1α), and toll-like receptor 4 (TLR4) were measured. Also, hepatic caspase 3, caspase 9, beclin-1, and c-Jun NH2-terminal kinase (JNK) in addition to serum alpha-fetoprotein (AFP) and α-L-Fucosidase (AFU) were assessed. Specimens of the liver were subjected to histopathological examination. Alogliptin and/or taxifolin induced significant improvement of liver function tests with significant increase in the survival rate, tissue antioxidant enzymes, Nrf2, caspase 3, caspase 9, Beclin-1 and JNK activities associated with significant decrease in serum AFP and AFU, tissue MDA, TGF-β1, IL-1α and TLR4 expression compared to HCC group. These results were significant with taxifolin/alogliptin combination when compared to the use of each of these agents alone. In conclusion, taxifolin/alogliptin combination might be used as adjuvant therapy for attenuation of HCC.

Collagen matrices attenuate the collagen-synthetic response of cultured fibroblasts to TGF-beta

1995 ◽  
Vol 108 (3) ◽  
pp. 1251-1261 ◽  
Author(s):  
R.A. Clark ◽  
L.D. Nielsen ◽  
M.P. Welch ◽  
J.M. McPherson
Keyword(s):  
Growth Factor ◽  
Granulation Tissue ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Collagen Matrix ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Collagen Gels ◽  
Type I Procollagen ◽  
Growth Factor Beta

Transforming growth factor-beta, a potent modulator of cell function, induces fibroblasts cultured on plastic to increase collagen synthesis. In 5- and 7-day porcine skin wounds, which have minimal to moderate collagen matrix, respectively, transforming growth factor-beta and type I procollagen were coordinately expressed throughout the granulation tissue. However, in 10-day collagen-rich granulation tissue type I procollagen expression diminished despite persistence of transforming growth factor-beta. To investigate whether collagen matrix attenuates the collagen-synthetic response of fibroblasts to transforming growth factor-beta, we cultured human dermal fibroblasts in conditions that simulate collagen-rich granulation tissue. Therefore, human dermal fibroblasts were suspended in attached collagen gels and collagen and noncollagen production was assayed in the absence and presence of transforming growth factor-beta. Although transforming growth factor-beta stimulated collagen synthesis by fibroblasts cultured in the collagen gels, these fibroblasts consistently produced less collagen than similarly treated fibroblasts cultured on plastic. This phenomenon was not secondary to nonspecific binding of transforming growth factor-beta to the collagen matrix. Fibroblasts cultured in a fibrin gel responded to transforming growth factor-beta similarly to fibroblasts cultured on plastic. Using immunofluorescence probes to type I procollagen, we observed that transforming growth factor-beta increased type I procollagen expression in most fibroblasts cultured on plastic, but only in occasional fibroblasts cultured in collagen gels. From these data we conclude that collagen matrices attenuate the collagen synthetic response of fibroblast to transforming growth factor-beta in vitro and possibly in vivo.

Transforming Growth Factor Beta 1 Serum Levels in Patients with Preinvasive and Invasive Lesions of the Breast

2004 ◽  
Vol 19 (3) ◽  
pp. 236-239 ◽  
Author(s):  
A. Lebrecht ◽  
C. Grimm ◽  
G. Euller ◽  
E. Ludwig ◽  
E. Ulbrich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Serum Levels ◽  
Breast Carcinogenesis ◽  
Receptor Status ◽  
Healthy Women ◽  
Growth Factor Beta ◽  
Tgf Β1

Transforming growth factor beta (TGF-β)1 is thought to be involved in breast carcinogenesis. TGF-β1 acts in an antiproliferative manner in the early stages of breast carcinogenesis, but promotes tumor progression and metastases in the advanced stages of the disease. No data have been published on serum TGF-β1 in breast cancer. We investigated TGF-β1 serum levels in patients with breast cancer (n=135), ductal carcinoma in situ (DCIS) I to III (n=67) or fibroadenoma (n=35), and in healthy women (n=40) to determine its value as a differentiation marker between malignant, pre-invasive and benign diseases and as a predictive marker for metastatic spread. Median (range) TGF-β1 serum levels in patients with breast cancer, DCIS I-III or benign breast lesions and in healthy women were 48.8 (18–82.4) pg/mL, 45.3 (26.9–58.3) pg/mL, 47.2 (17.2–80.5) pg/mL and 51.6 (30.9–65.1) pg/mL, respectively (p=0.2). In breast cancer patients TGF-β1 serum levels showed no statistically significant correlation with tumor stage, lymph node involvement, histological grade, estrogen receptor status and progesterone receptor status. Our data fail to indicate any correlation between serum TGF-β1 levels and clinicopathological parameters of breast diseases. Serum TGF-β1 levels do not provide clinical information in addition to established tumor markers.

Sign in / Sign up

Export Citation Format

Share Document