miR-31, miR-155, and miR-221 expression profiles and their association with graft skin tolerance in a syngeneic vs. allogeneic murine skin transplantation model

Author(s):  
Edna Ayerim Mandujano-Tinoco ◽  
Francisco González-García ◽  
Rosa M Salgado ◽  
René Fernando Abarca-Buis ◽  
José Manuel Sanchez-Lopez ◽  
...  

Abstract Grafting is the gold standard for the treatment of severe skin burns. Frequently, allogeneic tissue is the only transient option for wound coverage, but their use risks damage to surrounding tissues. MicroRNAs have been associated with acute rejection of different tissues/organs. In this study, we analyzed the expression of miR-31, miR-155, and miR-221 and associate it with graft tolerance or rejection using a murine full-thickness skin transplantation model. Recipient animals for the syngeneic and allogeneic groups were BALB/c and C57BL/6 mice, respectively; donor tissues were obtained from BALB/c mice. After 7 days post-transplantation (DPT), the recipient skin and grafts in the syngeneic group maintained most of their structural characteristics and transforming growth factor (TGF)β1 and TGFβ3 expression. Allografts were rejected early (Banff grades II and IV at 3 and 7 DPT, respectively), showing damage to the skin architecture and alteration of TGFβ3 distribution. miRNAs skin expression changed in both mouse strains; miR-31 expression increased in the recipient skin of syngeneic grafts relative to that of allogeneic grafts at 3 and 7 DPT (p < 0.05 and p < 0.01, respectively); miR-221 expression increased in the same grafts at 7 DPT (p < 0.05). The only significant difference between donor tissues was observed for miR-155 expression at 7 DPT which was associated with necrotic tissue. Only miR-31 and miR-221 levels were increased in the blood of BALB/c mice that received syngeneic grafts after 7 DPT. Our data suggest that local and systemic miR-31 and miR-221 overexpression are associated with graft tolerance.

Cardiology ◽  
2015 ◽  
Vol 131 (2) ◽  
pp. 97-106 ◽  
Author(s):  
Weili Qiao ◽  
Cheng Wang ◽  
Bing Chen ◽  
Fan Zhang ◽  
Yaowu Liu ◽  
...  

Objective: To investigate the effects of ibuprofen on cardiac fibrosis in a rat model of type 1 diabetes. Methods: The diabetic model was established by injecting streptozotocin into the rats. Then, ibuprofen or pioglitazone was given by gavage for 8 weeks. The cardiac fibrosis was assessed, and the major components of the renin-angiotensin system, the transforming growth factor β1 (TGF-β1) and the mammalian target of rapamycin (mTOR), were evaluated by histopathological, immunohistochemical, Western blot analysis or ELISA assay. Results: Obvious cardiac fibrosis was detected in the diabetic group and was alleviated by ibuprofen treatment. Angiotensin-converting enzyme (ACE), angiotensin (Ang) II and AngII type 1 receptor (AT1-R) levels were higher, and ACE2, Ang(1-7) and Mas receptor (Mas-R) were lower in the diabetic group. The ratio of ACE to ACE2 was raised in the diabetic group. All these changes were ameliorated by ibuprofen. TGF-β1 and mTOR were raised in the hearts of the diabetic group and were attenuated by ibuprofen treatment. There was no significant difference between the ibuprofen and the pioglitazone groups. Conclusion: Ibuprofen could ameliorate the cardiac fibrosis in diabetic rats by reduction of the ACE/AngII/AT1-R axis and enhancement of the ACE2/Ang(1-7)/Mas-R axis, leading to a decrease in TGF-β1 and mTOR.


Cephalalgia ◽  
2009 ◽  
Vol 29 (3) ◽  
pp. 365-372 ◽  
Author(s):  
SH Bø ◽  
EM Davidsen ◽  
P Gulbrandsen ◽  
E Dietrichs ◽  
G Bovim ◽  
...  

Cytokines have been measured in cerebrospinal fluid (CSF) from headache patients [infrequent episodic tension-type headache (TTH) and migraine with or without aura, all during attack, and cervicogenic headache] and compared with levels in pain-free individuals. Both proinflammatory [interleukin (IL)-1β, tumour necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1)] and anti-inflammatory cytokines IL-1 receptor antagonist (IL-1ra), IL-4, IL-10 and transforming growth factor-β1 (TGF-β1)] were included. There were significant group differences in IL-1ra, TGF-β1 and MCP-1 in episodic TTH and migraine compared with controls, and a significant difference in MCP-1 between cervicogenic headache and migraine with aura. Intrathecal MCP-1 correlated with IL-1ra, IL-10 and TGF-β1 in episodic TTH, and MCP-1 with IL-10 in migraine with aura. Cytokine increases were modest compared with those often accompanying serious neurological conditions, and may represent a mild response to pain. We believe this to be the first comparative study of CSF cytokine levels in connection with headache.


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 <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<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<0.001). After 4-days treatment with HD-DXM, the numbers of CD4+ CD25+ T cells (P<0.001), CD4+CD25high T cells ( P<0.001), and CD4+FOXP3+ T cells ( P<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<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>0.05) and there was no remarkable change of IL-10 in patients after HD-DXM treatment (P>0.05). The mRNA levels of Foxp3 and TGF-β1 gene in patients were lower than those of controls (P<0.05 and P<0.05); HD-DXM administration significantly increased the expressions of Foxp3 and TGF-β1 gene(P<0.05 and P<0.0001), which were even higher than those of controls(P<0.05 and P<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.


2014 ◽  
Vol 306 (7) ◽  
pp. G575-G581 ◽  
Author(s):  
Lihong Chen ◽  
Lin Zheng ◽  
Wubing He ◽  
Minglian Qiu ◽  
Lingyun Gao ◽  
...  

Dendritic cells transfected with interleukin (IL)-10 and transforming growth factor-β1 (TGF-β1) enhance T cell immunity and tolerance. However, no quantitative studies have investigated the suppressive functions of immature dendritic cells (imDC) cotransfected with IL-10 and TGF-β1. The effects of imDC cotransfected with IL-10 and TGF-β1 (IL-10-TGF-β1-imDC) on immune tolerance induction in a rat transplantation model were investigated. In addition, effects of IL-10-TGF-β1-imDC relative to IL-10-transfected imDC (IL-10-imDC) and TGF-β1-transfected imDC (TGF-β1-imDC) were compared. The infusion of IL-10-TGF-β1-imDC into recipients prolonged liver graft survival, which was sustained for >90 days. IL-12 serum levels decreased, whereas alanine transaminase and total bilirubin slightly increased in rats infused with IL-10-TGF-β1-imDC compared with the IL-10-imDC and TGF-β1-imDC groups. Furthermore, a higher percentage of terminal transferase-mediated UTP nick end-labeling-positive cells was observed, and histological analysis of the allografts indicated a rejection activity index of mild acute rejection. Our results suggest infusion of IL-10 and TGF-β1 cotransfected imDC induces alloantigen-specific T cell hyporesponsiveness, inhibits antigen-specific immunological responses to liver allografts, prolongs liver allograft survival, and enhances the immune tolerance. This approach may provide a promising alternative for enhancing donor-specific tolerance during liver transplantation.


2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Shahram Bamdad ◽  
Fatemeh Sanie-Jahromi ◽  
Marzieh Alamolhoda ◽  
Nasrin Masihpour ◽  
Mohammad-Hossein Karimi

Background. To investigate the association of glutathione s-transferase omega 2 (GSTO2) (142N > D) and transforming growth factor-β1 (TGF-β1) (869T > C) gene polymorphisms on the pathogenesis of two common types of glaucoma (including primary open-angle glaucoma (POAG) and chronic angle-closure glaucoma (CACG)) in the Iranian population. Methods. A total of 100 glaucoma patients (60% males and 40% females with an age mean ± SD of 34.66 ± 14.25 years; 56 cases of POAG and 44 cases of CACG) were enrolled in this study. GSTO2 (142N > D) and TGF-β1 (869T > C) polymorphisms were evaluated by PCR-based methods in patients and controls. Results. At locus GSTO2 (142N > D), the odds of ND genotype with respect to DD and NN genotypes were 1.55 and 2.08 times higher in POAG and CACG patients compared to those of patients in the control group (95% CI1: 0.80–2.98; 95% CI2: 1.00–4.33) which was statistically significant in CACG patients. However, the odds of DD and NN genotypes against the reference genotype in two patients group were not statistically significant as compared to those of patients in the control group. There was a significant association between the ND genotype and male patients (OR = 2.28, 95% CI: 1.06–4.92). The analysis of TGF-β1 (869T > C) polymorphisms showed no significant difference between the genotypes of TGF-β1 (869T > C) polymorphisms in patients and control groups; however, the CT genotype of TGF-β1 significantly differed between female controls and patients (OR = 0.42, 95% CI: 0.18–0.96). Conclusion. The presented results revealed that there was a significant association between the ND genotype of GSTO2 and the pathogenesis of glaucoma. Furthermore, this genotype can be considered as a sex-dependent genetic risk factor for the development of glaucoma. In contrast, the CT genotype of TGF-β1 is suggested to be a protective genetic factor against the pathogenesis of glaucoma.


2000 ◽  
Vol 11 (10) ◽  
pp. 1889-1895
Author(s):  
MASAHISA FUJISAWA ◽  
REIKO HARAMAKI ◽  
HIROSHI MIYAZAKI ◽  
TSUTOMU IMAIZUMI ◽  
SEIYA OKUDA

Abstract. Atherosclerotic vascular disease is a major cause of death for uremic patients who are on hemodialysis (HD). Recent evidence suggests that lipoprotein (a) [Lp(a)] may aggravate atherosclerosis by inhibiting activation of transforming growth factor-β1 (TGF-β1). Plasma Lp(a) and plasma TGF-β1 activation in HD patients (n = 51), chronic renal failure patients not subjected to hemodialysis (non-HD-CRF; n = 12), and healthy volunteers (control; n = 13) were investigated. Plasma Lp(a) was significantly higher in HD (18.75 ± 1.62 mg/ml) and non-HD-CRF patients (25.0 ± 8.4 mg/ml) than in control subjects (10.9 ± 5.8 mg/ml). The degree of atherosclerosis in HD patients was assessed by measuring the intima-media thickness (IMT) and plaque score with the use of an ultrasound scanner. IMT and plaque score were higher in HD and non-HD-CRF patients than in controls. A significant positive correlation was found in HD patients between Lp(a) and IMT (r = 0.377, P < 0.01) as well as between Lp(a) and plaque score (r = 0.43, P < 0.01). Plasma total TGF-β1 significantly increased in HD (119.8 ± 53.5 ng/ml) and non-HD-CRF patients (93.2 ± 25.0 ng/ml) compared with control subjects (17.7 ± 6.4 ng/ml), whereas the plasma level of mature (active) TGF-β1 did not differ among the groups. When plasma TGF-β1 and supernatant TGF-β1 from cultured peripheral mononuclear cells were compared before and after an HD session, neither total nor mature TGF-β1 showed a significant difference between the values before and after an HD session. There were no significant relationships between plasma total TGF-β1 and IMT or plaque score, between mature TGF-β1 and IMT or plaque score, or between mature TGF-β1 and Lp(a). In conclusion, Lp(a) may be an important atherogenic factor in CRF patients. However, it was not clarified whether Lp(a) exerts its effect by inhibiting TGF-β1 activation in CRF patients.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Xiaoying Zhang ◽  
Shasha Yu ◽  
Wencai Chen ◽  
Jianfei Ren ◽  
Xiaofeng Chen

Background and Objective: Isolated systolic hypertension (ISH) is characterized by increased aortic stiffness and associated with a significantly increased risk of cardiovascular morbidity and mortality. It has been reported that elevated plasma transforming growth factor-beta 1(TGF-β1)levels predicted development of hypertension. However, little is known about the association of TGF- β 1 pathway gene polymorphisms and ISH. The aim of the present study was to study the association of transforming growth factor-beta 1(TGF-β1)and its receptor 2(TGFBR2)functional gene polymorphisms with isolated systolic hypertension (ISH). Methods and Results: One hundred and three consecutive ISH patients and 169 healthy controls were recruited in this study. All subjects were genotyped for TGFβ1-869T/C, TGFBR2-3779A/G and TGFBR2-1444C/G by the technology of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and then confirmed by direct sequencing. No significant difference in genotype (and allele) frequency of TGFβ1-869T/C, TGFBR2-3779A/G and TGFBR2-1444C/G polymorphisms were observed between ISH group and healthy group (p>0.05). Conclusion: Our findings suggest that TGFβ1-869T/C, TGFBR2-3779A/G and TGFBR2-1444C/G polymorphisms may not be associated with susceptibility of isolated systolic hypertension in Chinese population.


2006 ◽  
Vol 291 (4) ◽  
pp. H1952-H1958 ◽  
Author(s):  
Martin D. Jarvis ◽  
Miriam T. Rademaker ◽  
Leigh J. Ellmers ◽  
Margaret J. Currie ◽  
Judith L. McKenzie ◽  
...  

This study investigated whether gene expression profiles of myofibroblasts derived from infarcted myocardium differ from normal cardiac fibroblasts. We compared the expression of cytoskeletal proteins in cultured ovine cardiac fibroblasts derived from infarcted (ID) and noninfarcted ovine myocardium (NID) and the levels of expression of the natriuretic peptide receptors (NPR)-A and NPR-B in response to treatment with transforming growth factor (TGF)-β1 and/or platelet-derived growth factor (PDGF). Transformation of cultured cardiac fibroblasts to myofibroblasts, as indicated by α-smooth muscle actin and vimentin expression, was independent of the presence of TGF-β1, PDGF, or cell origin. ID fibroblasts had higher basal levels than NID fibroblasts of NPR-A (ID: 58.0 ± 32.2 arbitrary density units, NID: undetectable), NPR-B (ID: 780 ± 155, NID: 330 ± 38 arbitrary density units) and collagen I (ID: 17.2 ± 0.5, NID: 10.5 ± 1.7 pg mRNA/μg total RNA, P < 0.05) but lower levels of α-SMa expression (ID: 50.2 ± 7.9, NID: 76.9 ± 3.2 fluorescence units, P < 0.05). NPR-A mRNA in ID fibroblasts showed a rapid fourfold increase in response to TGF-β1 and/or PDGF at 4 and 2 h, respectively, followed by a profound decline; in NID cells, NPR-A mRNA was undetectable. In ID fibroblasts, cytokines reduced NPR-B mRNA below control levels; in NID fibroblasts, TGF-β1 and PDGF elicited prompt increments in expression: a fourfold increase with TGF-β1 at 8 h and a twofold increase with PDGF at 4 h ( P < 0.05). In summary, transformation of cardiac fibroblasts to myofibroblasts in culture is independent of cytokine treatment. Moreover, whether the cultured cardiac fibroblasts are from infarct tissue is a major determinant of NPR expression levels and cytokine responses, even after four to five passages.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Natalia Zaicova ◽  
Tatiana Sudareva ◽  
Vladimir Dlin ◽  
Lilia Sinitsina ◽  
Anatolii Korsunskiy

Abstract Background and Aims to determine the diagnostic value of profibrogenic cytokines of transforming growth factor (TGF-β1) and angiotensin II (AngII) in urine to detect the severity of tubulointerstitial fibrosis in children with vesicoureteral reflux (VUR) depending on the therapeutic approach. Method 117 patients aged 3 to 16 years (mean age 10.2 ± 4.5, 70.1% of girls) with VUR were examined. The control group consisted of 20 healthy children. All children underwent a complete nephrological examination. The levels of TGF-β1 and AngII were determined in morning urine using the ELISA method and counted for urine creatinine. To identify the severity of the lesion of the renal parenchyma, a static DMSA scintigraphy was performed. Results depending on the therapeutic approach, the children were divided into 2 groups: 1 gr. - children on conservative treatment (63.2%), 2 gr. - children, after surgical correction of VUR (36.8%). In each group, 3 subgroups were identified depending on the development of tubulo-interstitial fibrosis according to DMSA: A subgr. - without signs of sclerosis (15.4%), B subgr. - 1-2 foci (44.74%) and C subgr - &gt; 3-4 foci of sclerosis (40.1%). All patients with VUR had a high urinary excretion of TGF-β1/Cr and AngII/Cr when compared with the control group (p&lt;0.05). Regardless of the therapeutic approach, in subgroups A (without foci of sclerosis) and B (1-2 foci of sclerosis), patients had a statistically significantly lower level of excretion of these cytokines when compared with patients from subgroup C (p &lt;0.05). No significant difference was found in the urinary excretion of TGF-β1/Cr and AngII/Cr depending on the therapeutic approach. Conclusion we established a reliable dependence of the excretion of TGF-β1/Cr and AngII /Cr in the urine on the severity of tubulo-interstitial fibrosis according to DMSA scintigraphy in children with VUR. At the same time, we did not note the dependence of the excretion of TGF-β1/Cr and AngII/Cr in the urine on the method of the therapeutic approach. Therefore, the study of the excretion of TGF-β1/Cr and AngII/Cr in the urine as non-invasive markers can be used as a criterion for the progression of nephropathy in VUR, regardless of treatment methods.


2011 ◽  
Vol 24 (02) ◽  
pp. 122-125 ◽  
Author(s):  
M. Stief ◽  
J. Gottschalk ◽  
J.-C. Ionita ◽  
A. Einspanier ◽  
G. Oechtering ◽  
...  

Summary Objectives: To report the concentration of blood cells and selected growth factors in canine autologous conditioned plasma (ACP). Methods: The density of blood cells in whole blood (WB), ACP and standard plasma preparation (SP) of 10 healthy mature dogs was determined. In both ACP and SP, the concentration of insulin-like growth factor-1 (IGF-1), epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor-AA, platelet-derived growth factor-AB, platelet-derived growth factor-BB, transforming growth factor-β1 (TGF-β1), and transforming growth factor-β2 was measured using the ELISA technique. In another ten dogs, ACP was prepared using an ultra-soft spinning protocol, and again blood cell density was compared to that obtained in WB. Results: The density of platelets in ACP was significantly higher than that in SP (p = 0.0002), but there was not any significant difference between ACP and WB, nor between WB and ACP prepared using softer centrifugations. Interestingly, only for IGF-1, PDGFBB, and TGF-β1 could reliable measurements be obtained, showing a significant increase in PDGF-BB and TGF-β1 concentrations in ACP compared to SP (p = 0.001, p = 0.0028). Regarding IGF-1 content, there was not any significant difference between ACP and SP. Clinical significance: Canine ACP prepared according to the manufacturer’s recommendations, or by using a softer spin does not show the same specifications as human ACP, which shows a doubling in platelet count compared to WB. Even though canine ACP has a similar number of platelets per injected volume and consequently, probably the same amount of injected growth factors than WB, application of canine ACP would not be associated with the proinflammatory potential reported for WB, as it is almost free of erythrocytes and nucleated cells.


Sign in / Sign up

Export Citation Format

Share Document