scholarly journals Biochemical mechanisms of skin radiation burns inhibition and healing by the volumetric autotransplantation of fibroblasts and of keratinocytes with fibroblasts composition

2015 ◽  
Vol 6 (2) ◽  
pp. 125-132
Author(s):  
L. V. Altukhova ◽  
K. V. Kot ◽  
Y. G. Kot ◽  
K. S. Morozova ◽  
Y. E. Persky

Mechanisms of influence of volumetric autotransplantation of fibroblasts and of the mixture of fibroblasts and keratinocytes on the development of the local 3rd degree X-ray burn and the radiation skin ulcer in guinea pigs were investigated. We used deepadministration into the irradiation zone on its perimeter of 6 doses, which contained (150–160)×103 fibroblasts and (130–140)×103 keratinocytes in 100 µl. It is shown that this autotransplantation carried out 1 hour after the irradiation, and then every 24 hours, reduces the area of burn on the 35th day, compared to the control by 63%. Radiation ulcer appears on the 10th day after irradiation and is completely healed on the 25th day. With the same regimen of administration of only fibroblasts containing (200–210)×103 cells in 100 µl, these parameters of treatment were equal to 31% on 4th and 35th day, respectively. It is shown that as a result of radiation in the area of burn the level of gene expression of collagen types I and III, elastin, fibronectin, vinculin, decorin, hyaluronansynthases 1, 2, 3, matrix metalloproteinases 1, 2, 3, 7, 9 and hyaluronidase is reduced. Besides, in the burn area the level of gene expression of transforming growth factor α, fibroblast growth factors 1, 2, 8 and anti-inflammatory cytokines – interleukin 10 and transforming growth factor-β1 – is reduced, while the level of gene expression of proinflammatory cytokine (interleykin1β) increases. Both types of autotransplantation cause the growth of the expression level of all the structural genes and regulatory proteins of biopolymers and decrease in the expression level of interleukin 1β, which leads to activation of tissue regeneration and healing of the burn wound. Reasonsfor the higher efficiency of autotransplantation using the mixture of fibroblasts and keratinocytes compared to autotransplantation by fibroblasts only are both the larger total number of live cells regularly replacing dead cells in the burn area, and mutual stimulation of auto-fibroblasts and auto-keratinocytes to proliferate and to synthesize biologically active substances, i.e. cytokines and growth factors.

2002 ◽  
Vol 111 (10) ◽  
pp. 947-953 ◽  
Author(s):  
Shin-Ichi Ishimoto ◽  
Toshio Ishibashi

The participation of growth factors in wound healing of tympanic membranes (TMs) is established. To determine the possible role of these growth factors in normal healing, we examined the regulation of keratinocyte growth factor (KGF), transforming growth factor–α (TGF-α), and basic fibroblast growth factor (bFGF) messenger RNA (mRNA) expression in wounded TMs of glucocorticoid-treated rats; these rats have severe wound healing abnormalities. Induction of KGF, TGF-α, and bFGF mRNA expression after TM injury was significantly reduced in these rats. Moreover, we found that the average number of bromodeoxyundine-positive cells in a glucocorticoid-treated group was significantly lower than that in controls. The data suggest that reduced expression of these genes might be partially responsible for the wound healing defects seen in these animals. These results provide a possible explanation for the beneficial effect of exogenous KGF, TGF-α, or bFGF in treatment of wound healing disorders of the TM.


2004 ◽  
Vol 128 (1) ◽  
pp. 68-70
Author(s):  
Yun-Cai Cai ◽  
Victor Roggli ◽  
Eugene Mark ◽  
Philip T. Cagle ◽  
Armando E. Fraire

Abstract Background.—Growth factors such as transforming growth factor α (TGF-α) and epidermal growth factor receptor (EGFR) play an important role in cell proliferation. The immunohistochemical expression of these factors has been extensively studied in malignant tumors including mesothelioma. However, the comparative expression of these growth factors in mesothelioma and reactive mesothelial proliferations has been less well studied. Objective.—To evaluate the possible role of TGF-α and EGFR in the clinically important distinction between reactive mesothelial proliferations and malignant mesothelioma. Methods.—The expression of TGF-α and EGFR was studied in 39 cases of mesothelioma and 30 cases of reactive mesothelial proliferations by means of immunohistochemistry. Results.—Fourteen (70%) of 20 reactive mesothelial proliferations tested and 29 (76%) of 38 mesotheliomas tested expressed TGF-α. One (3%) of 30 reactive mesothelial proliferations and 17 (45%) of 39 mesotheliomas expressed EGFR. Conclusions.—These results suggest an up-regulation of EGFR in mesothelioma as compared with reactive mesothelial proliferations. This up-regulation further suggests a possible use of EGFR as an adjunct immunohistochemical test in the differential diagnosis of mesothelioma and reactive mesothelial proliferations.


1999 ◽  
Vol 277 (5) ◽  
pp. L975-L982 ◽  
Author(s):  
A. Churg ◽  
B. Gilks ◽  
J. Dai

Respirable ambient particles [particulate matter <10 μm (PM10)] are associated with both acute and chronic adverse health effects including chronic airflow obstruction. PM10 can induce expression of inflammatory and fibrogenic mediators, but there is controversy about the types and/or sizes of particles involved and, in particular, whether ultrafine particles are the major toxic agents. To examine whether particle size affects mediator generation, we exposed rat tracheal explants, an inflammatory cell-free model of the airway wall, to various concentrations up to 500 μg/cm2 of fine (0.12 μm) or ultrafine (0.021 μm) titanium dioxide (anatase), maintained the explants in an organ culture in air for 1–7 days, and used RT-PCR to examine the expression of fibrogenic mediators and procollagen. No increase in gene expression was seen at 1 or 3 days, but at 5 days, ultrafine dust induced a small increase in procollagen. At 7 days, fine titanium dioxide produced significantly greater increases for platelet-derived growth factor (PDGF)-B, transforming growth factor-α, and transforming growth factor-β compared with those by ultrafine dust; both dusts produced similar increases for PDGF-A; and ultrafine dust produced increases in procollagen expression, whereas fine dust had no effect. Expression levels were dose related. Both dusts produced a similar decrease in expression of PDGF receptor-α and a similar increase in PDGF receptor-β. These observations suggest that ultrafine particles are intrinsically able to induce procollagen expression even in the absence of inflammatory cells; that chronic exposure to PM10 may result in chronic airflow obstruction, in part because of ultrafine particle-mediated increases in airway wall fibrosis; and that chemically identical dusts of differing size can produce quite different patterns of gene expression in the airway wall. Differential upregulation of PDGF receptors does not appear to explain dust-induced fibrosis in this model.


Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2207
Author(s):  
Jaume Gardela ◽  
Amaia Jauregi-Miguel ◽  
Cristina A. Martinez ◽  
Heriberto Rodríguez-Martinez ◽  
Manel López-Béjar ◽  
...  

The maternal environment modulates immune responses to facilitate embryo development and ensure pregnancy. Unraveling this modulation could improve the livestock breeding systems. Here it is hypothesized that the exposure of the female rabbit reproductive tract to semen, as well as to early embryos, modulates inflammation and angiogenesis among different tissue segments. qPCR analysis of the gene expression changes of the anti-inflammatory interleukin-10 (IL10) and transforming growth factor beta family (TGFβ1–3) and the angiogenesis mediator vascular endothelial growth factor (VEGF-A) were examined in response to mating or insemination with sperm-free seminal plasma (SP). Reproductive tract segment (cervix to infundibulum) samples were obtained in Experiment 1, 20 h after gonadotropin-releasing hormone (GnRH) stimulation (control), natural mating (NM) or vaginal infusion with sperm-free SP (SP-AI). Additionally, segmented samples were also obtained at 10, 24, 36, 68 or 72 h after GnRH-stimulation and natural mating (Experiment 2). The results of gene expression, analyzed by quantitative PCR, showed that NM effects were mainly localized in the uterine tissues, depicting clear temporal variation, while SP-AI effects were restricted to the oviduct. Changes in anti-inflammatory and angiogenesis mediators indicate an early response in the uterus and a late modulation in the oviduct either induced by semen or preimplantation embryos. This knowledge could be used in the implementation of physiological strategies in breeding systems to face the new challenges on rabbit productivity and sustainability.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Anna Zairi ◽  
Theodoros Lambrianidis ◽  
Ourania Pantelidou ◽  
Serafim Papadimitriou ◽  
Dimitrios Tziafas

The aim of this study was the comparative evaluation of inflammatory reactions and tissue responses to four growth factors, or mineral trioxide aggregate (MTA), or a zinc-oxide-eugenol-based cement (IRM) as controls, when used for the repair of furcal perforations in dogs’ teeth. Results showed significantly higher inflammatory cell response in the transforming growth factorβ1 (TGFβ1) and zinc-oxide-eugenol-based cement (IRM) groups and higher rates of epithelial proliferation in the TGFβ1, basic fibroblast growth factor (bFGF), and insulin growth factor-I (IGF-I) groups compared to the MTA. Significantly higher rates of bone formation were found in the control groups compared to the osteogenic protein-1 (OP-1). Significantly higher rates of cementum formation were observed in the IGF-I and bFGF groups compared to the IRM. None of the biologically active molecules can be suggested for repairing furcal perforations, despite the fact that growth factors exerted a clear stimulatory effect on cementum formation and inhibited collagen capsule formation. MTA exhibited better results than the growth factors.


1997 ◽  
Vol 14 (4) ◽  
pp. 218-222 ◽  
Author(s):  
Michiyoshi Taga ◽  
Hideya Sakakibara ◽  
Kumiko Suyama ◽  
Mario Ikeda ◽  
Hiroshi Minaguchi

2010 ◽  
Vol 30 (6) ◽  
pp. 460-469 ◽  
Author(s):  
Xiangdong Jian ◽  
Ming Li ◽  
Yijing Zhang ◽  
Yanjun Ruan ◽  
Guangran Guo ◽  
...  

Paraquat (PQ) can cause acute lung injury in humans and experimental animals. However, the role of growth factors in the progression of injury has not been clearly established. We developed an animal model of PQ-induced lung injury using Wistar rats. One milliliter of PQ solution (30, 60, and 120 mg/kg) was applied through the lavage, while the same amount of vehicle was applied to control rats. Based on histopathology, the lungs of some animals exposed to PQ showed acute fulmination, resulting in death, while others showed a more protracted injury, resulting in typical pulmonary fibrosis at 21 days. Using this PQ-poisoned rat model, we examined the intrapulmonary gene expression and circulatory level of cytokines and growth factors at 8 hours, 24 hours, 3 days, 7 days, 14 days, and 21 days after PQ administration. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the gene expression levels of interleukin-1 beta and interleukin-6 were significantly increased at 21 days after PQ challenge compared with the controls. The mRNA expression of tumor necrosis factor-alpha was also significantly increased except on days 14 and 21 after PQ treatment. Moreover, PQ-treated rats showed enhanced gene expression of growth factors such as platelet-derived growth factor-A and insulin-like growth factor-1 at 21 days and transforming growth factor-beta 1 at 14 days. ELISA results showed the circulatory level of cytokines and growth factors coincided with intrapulmonary gene expression. The synergistic effects of these molecules are presumed to cause pulmonary damage due to PQ challenge and may become targets of treatment.


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