scholarly journals The Role of Myofibroblasts in Granulomatous Lymphadenitis in Pigs Naturally Infected with M. Avium Subsp. Hominissuis

2018 ◽  
Vol 41 (1) ◽  
pp. 47-53
Author(s):  
Vladimir Polaček ◽  
Dejan Vidanović ◽  
Biljana Božić ◽  
Žolt Beckei ◽  
Ivana Vučićević ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Natural Infection ◽  
Interferon Γ ◽  
Transforming Growth Factor Β1 ◽  
Positive Tuberculin Skin Test ◽  
Type I ◽  
A Genome ◽  
Granulomatous Lymphadenitis ◽  
Tgf Β1

Abstract The most important morphological characteristic of infections caused by M. avium subsp. hominissuis (MAH) is granuloma formation. The growth of mycobacteria is in accordance with anti-bacterial effector mechanisms of the host within granuloma. The most important cytokines for „orchestrating“the host defense are interferon γ (INF-γ), tumor necrosis factor α (TNF-α) and transforming growth factor β1 (TGF-β1). Myofibroblasts that make up a peripheral layer of granuloma largely express receptors for TGF-β1. This cytokine is believed to affect the induction of myofibroblast proliferation. The aim of this paper is to point out the importance of myofibroblasts in the formation and sustainability of granuloma during natural infection of pigs with M. avium subsp. hominissuis. Examinations have been performed on the samples of Lnn. jejunales, Lnn. ileocolici and Lnn. colici of 100 pigs with a positive tuberculin skin test. The molecular method confirmed the presence of a genome M. avium subsp. hominissuis. The microscopic examination of lymph node samples stained by the routine hematoxyilin-eosin (HE) method, showed the presence of granulomatous lymphadenitis. The method of double immunohistochemical staining revealed that myofibroblasts which express TGF-β1 receptor type I (TGF-β1RI) and α smooth muscle actin (α SMA) have an important role in the morphogenesis of granulomatous lymphadenitis in pigs infected with MAH.

Angiotensin-(1–7) decreases the expression of collagen I via TGF-β1/Smad2/3 and subsequently inhibits fibroblast–myofibroblast transition

2016 ◽  
Vol 130 (21) ◽  
pp. 1983-1991 ◽  
Author(s):  
Jian Ping Zhou ◽  
Wei Tang ◽  
Yun Feng ◽  
Ning Li ◽  
Chen Juan Gu ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Renin Angiotensin System ◽  
Collagen Type I ◽  
Transforming Growth Factor Β1 ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Type I ◽  
Human Lung Fibroblast ◽  
Tgf Β1

Previous studies have shown that the RAS (renin–angiotensin system) might participate in airway remodelling in asthma. As a main component of the RAS, Ang-(1–7) [angiotensin-(1–7)] has been reported in few studies regarding its protective effect on asthma. However, the functional roles and relevant signalling pathways of Ang-(1–7) have not been well illustrated. In the present study, we analysed the effect of Ang-(1–7) on AngII (angiotensin II)-induced HLF (human lung fibroblast)–MF (myofibroblast) transition by detecting Col-I (collagen type I), TGF-β1 (transforming growth factor-β1) and α-SMA (α-smooth muscle actin) expression. We explored further the possible signalling pathways involved in HLF–MF transition. Our results showed that Ang-(1–7) could down-regulate the expression of Col-I, α-SMA and TGF-β1/Smad2/3 (all P<0.05). A significant decrease was found in phosphorylation of PI3K (phosphoinositide 3-kinase), Akt, p38-MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase) signalling pathways during HLF–MF transition (all P<0.05). Our data suggests that Ang-(1–7) decreases the expression of Col-I via TGF-β1/Smad2/3 and subsequently inhibits HLF–MF transition.

Abstract 3054: Comparison of Transforming Growth Factor-β1 Expression in Aortic Wall of Thoracic Aortic Aneurysm Versus Dissection

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Shouguo Yang ◽  
Guanggen Cui ◽  
Ramin Beygui ◽  
Fardad Esmailian ◽  
Abbas Ardehali ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Thoracic Aortic Aneurysm ◽  
Aortic Wall ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Underlying Mechanism ◽  
Transforming Growth Factor Β1 ◽  
Fluorescent Intensity ◽  
Nucleus Density ◽  
Tgf Β1

Background The underlying mechanism of thoracic aortic aneurysm (TAA) and dissection(TAD) was undetermined, and one controversy lies in whether they represent the different dvelopement period of the same disorder or totally diferent diseases. This study is in aim to compare the expression and distribution of Transforming Growth Factors(TGF) β1 in the aortic wall of TAA versus TAD patients. Method Aortic specimens were obtained from patients underwent to aortic procedures for TAA (n=38) and TAD (n=20) at UCLA , and control aorta (CN) from organ donnor (n=20). Double immunofluorescent stainning of TGF-β1 and α-smooth muscle actin were performed with paraffin embeded slides for all aortic samples and semiquantified by fluorescent intensity analysis. Histopathologic examination were performed with HE, Verhoeff van-Gieson and Masson’s trichrome stain. Results TAA and TAD patients exhibited an up-regulation of TGF-β1 to 120.3% and 109.6% compared with CN separately (P<0.05), with TAA higher than TAD (P<0.05). TGF-β1 distributed unevenly across aortic wall with the highest levels expression in tunica media, followed by intima then adventitia. In intima, TGF-β1 was expressed at the same level for TAD as CN, but was increased to 115.2% for TAA compared to CN (P<0.05). In media, TGF-β1 increased by 127.2% in TAA and 116.1% in TAD compared to CN (P<0.01), with TAA being higher than TAD (P<0.05). In adventitia, TGF- β1 was up-regulated to 119.6% and 116.7% for TAA and TAD compared to CN (P<0.05). Nucleus density analysis showed cellular plasia in adventitia of TAA and TAD than CN (P<0.05 ), while TAD patients demonstrated a higher nucleus density than TAA in intima and adventitia (P<0.05). α-actin was increased in media of TAA and TAD to 164.5% and 120% than CN (P<0.01 and P<0.05). Attenuated and interrupted elastin and mild to severe cystic medial degeneration were characteristic histopathologic finding in 29 (76.3%) TAA and 17(85%) TAD patients. Conclusions TGF- β1 expression was up-regulated in aortic wall of TAA and TAD compared to CN. The significant higher levels of TGF- β1 in intima and media in TAA versus TAD patients implicated a probable positive effect of TGF- β1 to maintain aortic wall integrity, and/or greater comsamption of TGF- β1 in the aortic dissection.

Histological and Biochemical Evaluation of Urethral Scar following Three Different Hypospadias Repairs: An Experimental Study in Rabbits

2017 ◽  
Vol 28 (05) ◽  
pp. 420-425 ◽  
Author(s):  
Xiao-Hui Tan ◽  
Chun-Lan Long ◽  
De-Ying Zhang ◽  
Tao Lin ◽  
Da-Wei He ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
White Male ◽  
Transforming Growth Factor Β1 ◽  
Rational Approach ◽  
Hypospadias Repair ◽  
Tubularized Incised Plate ◽  
Biochemical Evaluation ◽  
Tubularized Incised Plate Urethroplasty ◽  
Tgf Β1

Introduction Several urethroplasties have been employed in the surgical treatment of hypospadias. Neourethral strictures are among the most common postoperative complications that often require reoperation. Materials and Methods We created a hypospadias model in New Zealand white male rabbits through a hypospadias-like defect and acute repair. A total of 24 animals were randomly allocated into three groups: tubularized incised-plate urethroplasty (TIPU) group (8), perimeatal-based flap urethroplasty (Mathieu) group (8), onlay island flap urethroplasty (onlay) group (8), and corresponding surgical procedures were immediately performed to reconstruct neourethra. The rabbits were killed postoperatively at 5 days, 2 weeks, 6 weeks, and 3 months, respectively. The penile tissue was harvested for histological and biochemical investigations to evaluate the expressions of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMactin) in all groups. Results All rabbits were operated on uneventfully. The amount of collagen content was increased in the Mathieu and onlay groups than in the TIPU group (p < 0.05). Biochemical analysis showed that the expression of TGF-β1 in the TIPU group was decreased compared with the two other groups at 2 or 6 weeks postoperatively (p < 0.01). The expression pattern regarding α-SMactin was similar at 6 weeks or 3 months postoperatively (p < 0.01). Conclusion The neourethra repaired by TIPU was practically resumed to normal anatomy and scarring was less apparent than the two other groups. Therefore, TIPU is considered as a relatively rational approach for hypospadias repair. The activity of fibroblasts has been increased in the long term, which may be the pathogenesis of neourethral stricture following hypospadias repair.

scholarly journals Transforming growth factor-β1 up-regulates connexin43 expression in osteocytes via canonical Smad-dependent signaling pathway

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Wenjing Liu ◽  
Yujia Cui ◽  
Jianxun Sun ◽  
Linyi Cai ◽  
Jing Xie ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connexin 43 ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Underlying Mechanism ◽  
Transforming Growth Factor Β1 ◽  
Type I ◽  
Gap Junctional Intercellular Communication ◽  
Cx43 Expression ◽  
Tgf Β1

Connexin 43 (Cx43)-mediated gap junctional intercellular communication (GJIC) has been shown to be important in regulating multiple functions of bone cells. Transforming growth factor-β1 (TGF-β1) exhibited controversial effects on the expression of Cx43 in different cell types. To date, the effect of TGF-β1 on the Cx43 expression of osteocytes is still unknown. In the present study, we detected the expression of TGF-β1 in osteocytes and bone tissue, and then used recombinant mouse TGF-β1 to elucidate its effect on gap junctions (GJs) of osteocytes. Our data indicated that TGF-β1 up-regulated both mRNA and protein expression of Cx43 in osteocytes. Together with down-regulation of Cx43 expression after being treated with TGF-β type I receptor inhibitor Repsox, we deduced that TGF-β1 can positively regulate Cx43 expression in osteocytes. Thus we next focussed on the downstream signals of TGF-β and found that TGF-β1-mediated smads, Smad3 and Smad4, to translocate into nucleus. These translocated signal proteins bind to the promoter of Gja1 which was responsible for the changed expression of Cx43. The present study provides evidence that TGF-β1 can enhance GJIC between osteocytes through up-regulating Cx43 expression and the underlying mechanism involved in the activation of Smad-dependent pathway.

scholarly journals Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17

2020 ◽  
Vol 8 (B) ◽  
pp. 738-746
Author(s):  
Haryudi Aji Cahyono ◽  
Wisnu Barlianto ◽  
Dian Handayani ◽  
Handono Kalim
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Transforming Growth Factor Β1 ◽  
Premature Atherosclerosis ◽  
Ifn Γ ◽  
Tgf Β1

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.

scholarly journals IL-15 regulates fibrosis and inflammation in a mouse model of chronic pancreatitis

2018 ◽  
Vol 315 (6) ◽  
pp. G954-G965 ◽  
Author(s):  
Murli Manohar ◽  
Hemanth Kumar Kandikattu ◽  
Alok Kumar Verma ◽  
Anil Mishra
Keyword(s):  
Chronic Pancreatitis ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Interferon Γ ◽  
Cancer Tissue ◽  
Inkt Cells ◽  
Interleukin 15 ◽  
Potential Strategy ◽  
Tgf Β1

Pancreatitis is an inflammatory disease characterized by the induction of several proinflammatory cytokines like interleukin (IL)-6, IL-8, IL-1β, and IL-1. Recently, the multifunctional innate cytokine IL-15 has been implicated in the protection of several diseases, including cancer. Tissue fibrosis is one of the major problems in successfully treating chronic pancreatitis pathogenesis. Therefore, we tested the hypothesis that recombinant IL-15 (rIL-15) treatment may induce innate tissue responses and its overexpression will improve the pathogenesis of cerulein-induced chronic pancreatitis, associated remodeling, and fibrosis. We observed atrophy of acinar cells, increased inflammation, and increased deposition of perivascular collagen, the upregulated protein level of transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA), and collagen-1 in cerulein-induced chronic pancreatitis in mice. Furthermore, we reported that rIL-15 treatment protects mice from the cerulein-induced chronic pancreatitis pathogenesis, including acinar cell atrophy, and perivascular accumulation of tissue collagen followed by downregulation of profibrotic genes such as TGF-β1, α-SMA, collagen-1, collagen-3, and fibronectin in cerulein-induced chronic pancreatitis in mice. Mechanistically, we show that IL-15-mediated increase of interferon-γ-responsive invariant natural killer T (iNKT) cells in the blood and tissue protects cerulein-induced pancreatic pathogenesis in mice. Of note, a reduction in iNKT cells was also observed in human chronic pancreatitis compared with normal individuals. Taken together, these data suggest that IL-15 treatment may be a novel therapeutic strategy for treating chronic pancreatitis pathogenesis. NEW & NOTEWORTHY Pancreatic fibrosis is a major concern for the successful treatment of chronic pancreatitis and pancreatic cancer. Therefore, restriction in the progression of fibrosis is the promising approach to manage the pancreatitis pathogenesis. Herein, we present in vivo evidences that pharmacological treatment of recombinant interleukin-15 improves remodeling and fibrosis in cerulein-induced chronic pancreatitis in mice. Our observations indicate that interleukin-15 immunotherapy may be a possible and potential strategy for restricting the progression of fibrosis in chronic pancreatitis.

scholarly journals Fucoxanthin Inhibits Myofibroblast Differentiation and Extracellular Matrix Production in Nasal Polyp-Derived Fibroblasts via Modulation of Smad-Dependent and Smad-Independent Signaling Pathways

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 323 ◽  
Author(s):  
Hyun Jung ◽  
Dae-Sung Lee ◽  
Seong Park ◽  
Jung Choi ◽  
Won-Kyo Jung ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathways ◽  
Nasal Polyp ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Type I ◽  
Molecular Signaling ◽  
Tgf Β1

Nasal polyps (NPs) are a multifactorial disorder associated with a chronic inflammatory state of the nasal mucosa. Fucoxanthin (Fx) is a characteristic orange carotenoid obtained from brown algae and has diverse immunological properties. The present study investigated whether Fx inhibits fibrosis-related effects in nasal polyp-derived fibroblasts (NPDFs) and elucidated the molecular signaling pathways involved. The production of collagen type I (Col-1) was investigated in NP tissue via immunohistochemistry and western blot analysis. NPDFs were treated with transforming growth factor (TGF)-β1 (1 ng/mL) in the presence or absence of Fx (5–30 µM). The levels of α-smooth muscle actin (α-SMA), Col-1, and phosphorylated (p)-Smad 2/3, signal protein-1 (SP-1), MAPKs (mitogen-activated protein kinases), and Akt were measured by western blot analysis. The expression of Col-1 was detected in NP tissues. TGF-β1 stimulated the production of α-SMA and Col-1, and stimulated the contraction of collagen gel. However, pretreatment with Fx attenuated these effects. Furthermore, these inhibitory effects were mediated through modulation of both Smad 2/3 and Akt/SP-1 signaling pathways in TGF-β1-induced NPDFs. The results from the present study suggest that Fx may be a novel anti-fibrotic agent for the treatment of NP formation.

scholarly journals Smad7 Abrogates Transforming Growth Factor-β1-mediated Growth Inhibition in COLO-357 Cells through Functional Inactivation of the Retinoblastoma Protein

2005 ◽  
Vol 280 (23) ◽  
pp. 21858-21866 ◽  
Author(s):  
Nichole Boyer Arnold ◽  
Murray Korc
Keyword(s):  
Growth Factor ◽  
Growth Inhibition ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Retinoblastoma Protein ◽  
Transforming Growth Factor Β1 ◽  
Type I ◽  
Pancreatic Cancer Cells ◽  
Induced Apoptosis ◽  
Tgf Β1

Smad7 is overexpressed in 50% of human pancreatic cancers. COLO-357 pancreatic cancer cells engineered to overexpress Smad7 are resistant to the actions of transforming growth factor-β1 (TGF-β1) with respect to growth inhibition and cisplatin-induced apoptosis but not with respect to modulation of gene expression. To delineate the mechanisms underlying these divergent consequences of Smad7 overexpression, we studied the effects of Smad7 on TGF-β1-dependent signaling pathways and cell cycle regulating proteins. TGF-β1 induced the phosphorylation of MAPK, p38 MAPK, and AKT2 irrespective of the levels of Smad7, and inhibitors of these pathways did not alter TGF-β1 actions on cell growth. By contrast, Smad7 overexpression interfered with TGF-β1-mediated attenuation of cyclin A and B levels, inhibition of cdc2 dephosphorylation and CDK2 inactivation, up-regulation of p27, and the maintenance of the retinoblastoma protein (RB) in a hypophosphorylated state. Smad7 also suppressed TGF-β1-mediated inhibition of E2F activity but did not alter TGF-β1-mediated phosphorylation of Smad2, the nuclear translocation of Smad2/3/4, or DNA binding of the Smad2/3/4 complex. Although Smad7 did not associate with the type I TGF-β receptor (TβRI), SB-431542, an inhibitor of the kinase activity of this receptor, blocked TGF-β1-mediated effects on Smad-2 phosphorylation. These findings point toward a novel paradigm whereby Smad7 acts to functionally inactivate RB and de-repress E2F without blocking the activation of TβRI and the nuclear translocation of Smad2/3, thereby allowing for TGF-β1 to exert effects in a cancer cell that is resistant to TGF-β1-mediated growth inhibition.

Sign in / Sign up

Export Citation Format

Share Document