Localized temporal co-delivery of interleukin 10 and decorin genes using amediated by collagen-based biphasic scaffold modulates the expression of TGF-β1/β2 in a rabbit ear hypertrophic scarring model

2021 ◽  
Vol 9 (8) ◽  
pp. 3136-3149
Author(s):  
Ciarstan McArdle ◽  
Sunny Akogwu Abbah ◽  
Sirsendu Bhowmick ◽  
Estelle Collin ◽  
Abhay Pandit

The study shows that although pIL-10/pDCN therapy are individually able to suppress TGF-β1/β2, only the combined overexpression of both transgenes was efficacious in suppressing TGF-β1/β2 and concurrently sustaining the upregulation of TGF-β3.

2020 ◽  
Vol 8 (B) ◽  
pp. 738-746
Author(s):  
Haryudi Aji Cahyono ◽  
Wisnu Barlianto ◽  
Dian Handayani ◽  
Handono Kalim

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process. AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]). METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019). RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p < 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p < 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p < 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p < 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%). CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.


2012 ◽  
Vol 35 (11) ◽  
pp. 1999-2006 ◽  
Author(s):  
Dong Won Lee ◽  
Sae Kwang Ku ◽  
Hyuk Jun Cho ◽  
Jeong Hwan Kim ◽  
Tran Tuan Hiep ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Mohammad M. Al-Qattan ◽  
Mervat M. Abd-Al Wahed ◽  
Khalid Hawary ◽  
Ahmed A. Alhumidi ◽  
Medhat K. Shier

nAG (newt-Anterrior Gradient) protein is the key mediator of regrowth of amputated limbs in salamanders. In a previous work in our lab, a newnAGgene (suitable for humans) was designed and cloned. The cloned vector was transfected into primary human fibroblasts. The expression ofnAGin human primary fibroblasts was found to suppress collagen expression. The current study shows that local injection of recombinant nAG reduces scar hypertrophy in the rabbit ear model. This is associated with lower scar elevation index (SEI), lower levels of collagen I & III, higher levels of MMP1, and a higher degree of scar maturation in experimental wounds compared to controls.


2011 ◽  
Vol 49 (7) ◽  
pp. 764-769 ◽  
Author(s):  
Jian-Guo Wu ◽  
Yan-Jie Wei ◽  
Xia Ran ◽  
Hong Zhang ◽  
Hua Nian ◽  
...  

2017 ◽  
Vol 5 (6) ◽  
pp. e1294 ◽  
Author(s):  
Shengxian Jia ◽  
Ping Xie ◽  
Seok J. Hong ◽  
Robert D. Galiano ◽  
Thomas A. Mustoe

Author(s):  
M J Hussain ◽  
N Shaikh ◽  
R Francavilla ◽  
N Heaton ◽  
R Williams ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
D. Jiang ◽  
B. Guo ◽  
F. Lin ◽  
Q. Hui ◽  
K. Tao

Hypertrophic scarring is a skin collagen disease that can occur following skin damage and is unlikely to heal or subside naturally. Since surgical treatment often worsens scarring, it is important to investigate the pathogenesis and prevention of hypertrophic scarring. Thrombospondin-1 (THBS1) is a matrix glycoprotein that can affect fibrosis by activating TGF-β1, which plays a key role in wound repair and tissue regeneration; therefore, we investigated the effects of THBS1 on the biological function of hypertrophic scar fibroblasts. THBS1 expression was measured in hypertrophic scars and adjacent tissues as well as normal fibroblasts, normal scar fibroblasts, and hypertrophic scar fibroblasts. In addition, THBS1 was overexpressed or silenced in hypertrophic scar fibroblasts to determine the effects of THBS1 on cell proliferation, apoptosis, and migration, as well as TGF-β1 expression. Finally, the role of THBS1 in hypertrophic scarring was confirmed in vivo using a mouse model. We found that THBS1 expression was increased in hypertrophic scar tissues and fibroblasts and promoted the growth and migration of hypertrophic scar fibroblasts as well as TGF-β1 expression. Interestingly, we found that si-THBS1 inhibited the occurrence and development of bleomycin-induced hypertrophic scars in vivo and downregulated TGF-β1 expression. Together, our findings suggest that THBS1 is abnormally expressed in hypertrophic scars and can induce the growth of hypertrophic scar fibroblasts by regulating TGF-β1. Consequently, THBS1 could be an ideal target for treating hypertrophic scarring.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3920-3920
Author(s):  
Yun Ling ◽  
Xiangshan Cao ◽  
Ziqiang Yu ◽  
Changgeng Ruan

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disorder and high-dose dexamethasone (HD-DXM) has been used as a first-line therapy for patients with ITP. However, little is known about the role of CD4+CD25 + regulatory T (Treg) cells, interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in the pathogenesis of chronic ITP and the effects of HD-DXM on them contained Treg cells, IL-10 and TGF-β1. In this study, we investigated the expressions of Treg cells, IL-10 and TGF-β1 in 26 untreated adult patients with chronic ITP. All patients had thrombocytopenia (platelet count &lt;50 × 109/L) for more than 6 months. We also observed short time changes of Treg cells, IL-10 and TGF-β1 after treatment with HD-DXM in these patients. The results showed that a good initial response to HD-DXM occurred in 24 of the 26 patients with chronic ITP (92.3%): the mean platelet count was (84.9±30.4)×109/L [range, (20∼150) ×109/L] one week after the initiation of treatment. The proportion of CD4+CD25+ T cells in the peripheral blood of patients with chronic ITP was significantly higher than that in normal controls(P&lt;0.001); there was no significant difference in the percentage of CD4+CD25high T cells between patients and controls ( P=0.317); but the number of CD4+ FOXP3+ T cells in patients was significantly lower than that in controls (P&lt;0.001). After 4-days treatment with HD-DXM, the numbers of CD4+ CD25+ T cells (P&lt;0.001), CD4+CD25high T cells ( P&lt;0.001), and CD4+FOXP3+ T cells ( P&lt;0.001) in patients were all significantly increased. In the serum of chronic ITP patients, the expression level of TGF-β1 was lower than that of healthy controls (P&lt;0.0001) and HD-DXM could significantly increase it; there was no significant difference in the expression level of IL-10 between patients and controls ( P&gt;0.05) and there was no remarkable change of IL-10 in patients after HD-DXM treatment (P&gt;0.05). The mRNA levels of Foxp3 and TGF-β1 gene in patients were lower than those of controls (P&lt;0.05 and P&lt;0.05); HD-DXM administration significantly increased the expressions of Foxp3 and TGF-β1 gene(P&lt;0.05 and P&lt;0.0001), which were even higher than those of controls(P&lt;0.05 and P&lt;0.05); There was a positive correlation between the Foxp3 mRNA expression and TGF-β1 after treatment with HD-DXM (r =0.403, P=0.041). These results suggest that Foxp3 and TGF-β1 gene are deficient in chronic ITP and the immunosuppressive therapy of glucocorticoids could improve the expression levels of these genes.


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