scholarly journals A Polymeric Diet Rich in Transforming Growth Factor Beta 2 Does Not Reduce Inflammation in Chronic 2,4,6-trinitrobenzene Sulfonic Acid Colitis in Pre-pubertal Rats

2020 ◽  
Author(s):  
Claire Dupont-Lucas ◽  
Rachel Marion-Letellier ◽  
Mathilde Pala ◽  
Charlène Guérin ◽  
Asma Amamou ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Intestinal Inflammation ◽  
Growth Failure ◽  
Therapeutic Interventions ◽  
Male Rats ◽  
Trinitrobenzene Sulfonic Acid ◽  
Sprague Dawley ◽  
Chronic Colitis ◽  
Colon Wall

Abstract Background: Pediatric Crohn’s disease is characterized by a higher incidence of complicated phenotypes. Murine models help to better understand the dynamic process of intestinal fibrosis and test therapeutic interventions. Pre-pubertal models are lacking. We aimed to adapt a model of chronic colitis to pre-pubertal rats and test if a polymeric diet rich in TGF-β2 could reduce TNBS-induced intestinal inflammation and fibrosis. Methods: Colitis was induced in 20 five-week-old Sprague-Dawley male rats by weekly rectal injections of increasing doses of TNBS (90 mg/kg, 140 mg/kg and 180 mg/kg) for 3 weeks, while 10 controls received phosphate-buffered saline (PBS). Rats were anesthetized using ketamine and chlorpromazine. After first administration of TNBS, 10 rats were fed exclusively MODULEN IBD® powder, while remaining rats were fed breeding chow. Colitis was assessed one week after last dose of TNBS by histopathology and magnetic resonance colonography (MRC). Results: Histological inflammation and fibrosis scores were higher in TNBS group than controls (p<0.05 for both). MRC showed increased colon wall thickness in TNBS group compared to controls (p<0.01), and increased prevalence of strictures and target sign (p<0.05). Colon expression of COL1A1, CTGF, α-SMA and COX-2 did not differ between TNBS rats and controls. TNBS colitis was not associated with growth failure. Treatment with MODULEN IBD® was associated with growth failure, increased colon weight/length ratio (p<0.01), but did not affect histological scores or MRI characteristics. Colon expression of α-SMA was significantly lower in the MODULEN group vs. controls (p=0.005).Conclusion: Features of chronic colitis were confirmed in this model, based on MRC and histopathology. Treatment with MODULEN did not reverse inflammation or fibrosis.

scholarly journals A polymeric diet rich in transforming growth factor beta 2 does not reduce inflammation in chronic 2,4,6-trinitrobenzene sulfonic acid colitis in pre-pubertal rats

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Claire Dupont-Lucas ◽  
Rachel Marion-Letellier ◽  
Mathilde Pala ◽  
Charlène Guerin ◽  
Asma Amamou ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Intestinal Inflammation ◽  
Growth Failure ◽  
Group Versus ◽  
Therapeutic Interventions ◽  
Male Rats ◽  
Trinitrobenzene Sulfonic Acid ◽  
Chronic Colitis ◽  
Colon Wall

Abstract Background Pediatric Crohn’s disease is characterized by a higher incidence of complicated phenotypes. Murine models help to better understand the dynamic process of intestinal fibrosis and test therapeutic interventions. Pre-pubertal models are lacking. We aimed to adapt a model of chronic colitis to pre-pubertal rats and test if a polymeric diet rich in TGF-β2 could reduce TNBS-induced intestinal inflammation and fibrosis. Methods Colitis was induced in 20 five-week-old Sprague–Dawley male rats by weekly rectal injections of increasing doses of TNBS (90 mg/kg, 140 mg/kg and 180 mg/kg) for 3 weeks, while 10 controls received phosphate-buffered saline. Rats were anesthetized using ketamine and chlorpromazine. After first administration of TNBS, 10 rats were fed exclusively MODULEN IBD® powder, while remaining rats were fed breeding chow. Colitis was assessed one week after last dose of TNBS by histopathology and magnetic resonance colonography (MRC). Results Histological inflammation and fibrosis scores were higher in TNBS group than controls (p < 0.05 for both). MRC showed increased colon wall thickness in TNBS group compared to controls (p < 0.01), and increased prevalence of strictures and target sign (p < 0.05). Colon expression of COL1A1, CTGF, α-SMA and COX-2 did not differ between TNBS rats and controls. TNBS colitis was not associated with growth failure. Treatment with MODULEN IBD® was associated with growth failure, increased colon weight/length ratio (p < 0.01), but did not affect histological scores or MRI characteristics. Colon expression of α-SMA was significantly lower in the MODULEN group versus controls (p = 0.005). Conclusion Features of chronic colitis were confirmed in this model, based on MRC and histopathology. Treatment with MODULEN did not reverse inflammation or fibrosis.

scholarly journals EFFECTIVENESS AND MECHANISM OF PHYSICIAN HERBS FROM KALI PUTIH BATUR BANJARNEGARA CENTRAL JAVA AGAINST DIABETIC NEPHROPATHY

2018 ◽  
Vol 11 (12) ◽  
pp. 452
Author(s):  
Kintoko Kintoko ◽  
Hardi Astuti Witasari ◽  
Djati Wulan Kusumo ◽  
Halid Kapri ◽  
Tya Muldiyana ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Traditional Medicine ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Negative Control ◽  
Male Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Central Java ◽  
Cox 2

Objectives: Complications in the kidneys (nephropathy) are one of the chronic complications of diabetes mellitus (DM) most common microvascular and estimated to reach 30–40% of all sufferers of DM. Until now there is no cure drug that can prevent diabetic nephropathy. Therefore, the handling of this issue should be done seriously, one of them through an exploration of drug discovery and drug material. Ristoja in 2015 in the ethnic Javanese Banyumasan successfully explores the types of plants, herb, and traditional medicine culture. One is conducted by the Kaliputih Traditional Medicine, Batur, Banjarnegara, Central Java. Based on the results of the interview, traditional medicine has herb for disease therapy kidney failure which consists of 11 species of plants.Methods: The herbs were extracted by infundation method. Sprague Dawley albino male rats were divided into 3 groups (normal, positive, and negative) and 3 sample test groups with 3 different doses (18, 36, and 54 mL/kg body weight [BW]) previously induced streptozotocin. Observations were carried on the levels blood urea nitrogen (BUN), creatinine, uric acid, and nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), and transforming growth factor-beta (TGF-β) kidney immunohistochemically and histology analysis.Results: Statistical results showed a significant increase of BUN levels in all dose variation groups after being given herbs, compared to the negative control group. The result of the examination of biochemical parameters of creatinine levels statistic showed significant (p<0.05) decrease in the dose 18 and 36 mL/kg BW compare with the negative group. The result of the study on histopathology kidney organs there are are damages to each test in each organ that is necrosis. The result of NF-κB, COX-2, and TGF-β expression no significant decrease compared with the negative controls.Conclusion: The herbs are not capable of nephropathy diabetic and need more research to know that activity as nephroprotective.

scholarly journals Sedum sarmentosum Total Flavonoids Alleviate Schistosomiasis-Induced Liver Fibrosis by Altering TGF-β1 and Smad7 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Peng-chun Yang ◽  
Wei-zhe Bai ◽  
Jing Wang ◽  
Cai-hua Yan ◽  
Wei-feng Huang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Protein Expression ◽  
Hepatic Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Schistosomiasis Japonica ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Tgf Β1 ◽  
Liver Tissues

Objectives. Schistosomiasis is a parasitic disease that affects over 142 million people worldwide. The main causes of death of schistosomiasis include liver granuloma and secondary hepatic cirrhosis resulting from severe fibrosis. Despite intensive research, controlling liver fibrosis associated with schistosomiasis remains challenging. Sedum sarmentosum total flavonoid (SSTF) is a promising agent to reduce liver fibrosis with an unknown mechanism. Thus, the objectives of this study are to validate its effect on the liver fibrosis caused by schistosomiasis and to explore the underlying molecular mechanism. Methods. Sixty male Sprague-Dawley rats were randomly divided into six groups: one group of normal control and five groups of liver fibrosis induced by schistosomiasis japonica with or without SSTF or colchicine treatment, the latter serving as the positive control. Liver tissues from each animal were harvested to observe the degree and grade of hepatic fibrosis. We also measured the expression of transforming growth factor-beta 1 (TGF-β1) and Smad7 using RT-qPCR, Western blot, and immunohistochemistry. Results. Compared with the untreated model group, groups treated with SSTF at all three tested doses had significantly reduced hepatic fibrosis ( P < 0.05 ). Each dose of SSTF also significantly reduced TGF-β1 protein expression and mRNA levels in the liver tissues ( P < 0.05 ). In contrast, the middle and high doses of SSTF significantly increased Smad7 protein expression and mRNA levels ( P < 0.05 ). Immunohistochemistry showed that each dose of SSTF reduced TGF-β1 protein expression ( P < 0.05 ). Conclusion. Our results demonstrated that SSTF alleviated schistosomiasis japonica-induced hepatic fibrosis by inhibiting the TGF-β1/Smad7 pathway.

Correlation of the Expression of IGF-1, TGF-β1 and BMP12 with Tendon Degeneration Caused by Overused Tendon of the Long Head of Biceps Brachii

2019 ◽  
Vol 9 (6) ◽  
pp. 778-782
Author(s):  
Chongbin Fang ◽  
Haibin Yan ◽  
Xinhui Guo ◽  
Liming Wang
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Biceps Brachii ◽  
Small Animal ◽  
Normal Group ◽  
Sprague Dawley ◽  
Tendon Degeneration ◽  
Long Head Of Biceps ◽  
Long Head

Objective: To assess the association of the expression of insulin-like growth factor-1 (IGF-1), transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein-12 (BMP-12) with tendon degeneration in rats caused by overuse of biceps brachii long head tendon. Methods: Sixteen Sprague-Dawley (SD) rats were randomly divided into normal group (n = 8) and overuse group (n = 8). Rats were fed routinely in normal group and were treated by small animal treadmills for continuous 6 weeks of exercise at 1 h/day in overuse group followed by analysis of histological morphology of the tendon of the long head of biceps brachii by Hematoxylin-eosin (HE) staining, the expression levels of IGF-1, TGF-β1 and BMP-12 by Western blotting. Correlation analysis was used to analyze the correlation of the protein expression with the pathological score. Results: HE staining showed normal morphology of biceps brachii long head tendon in normal group (with dense structure, uniform arrangement and no fiber damage) and abnormal morphology in overuse group (with disordered structure, uneven arrangement and some of breakage fibers). The pathological score in overuse group was significantly higher than that in normal group (p < 0.05). Compared with those in normal group, the protein levels of IGF-1, TGF-β1 and BMP-12 were significantly elevated in overuse group (p < 0.05). Conclusion: The expression of IGF-1, TGF-β1 and BMP-12 in overused tendon of the long head of the biceps brachii are elevated, and positively correlated with tendon degeneration.

scholarly journals Ghrelin Ameliorates Angiotensin II-Induced Myocardial Fibrosis by Upregulating Peroxisome Proliferator-Activated Receptor Gamma in Young Male Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Qian Wang ◽  
Xin Sui ◽  
Rui Chen ◽  
Pei-Yong Ma ◽  
Yong-Liang Teng ◽  
...  
Keyword(s):  
Myocardial Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Male Rats ◽  
Peroxisome Proliferator ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Collagen Iii

Angiotensin (Ang) II contributes to the formation and development of myocardial fibrosis. Ghrelin, a gut peptide, has demonstrated beneficial effects against cardiovascular disease. In the present study, we explored the effect and related mechanism of Ghrelin on myocardial fibrosis in Ang II-infused rats. Adult Sprague-Dawley (SD) rats were divided into 6 groups: Control, Ang II (200ng/kg/min, microinfusion), Ang II+Ghrelin (100μg/kg, subcutaneously twice daily), Ang II+Ghrelin+GW9662 (a specific PPAR-γinhibitor, 1 mg/kg/d, orally), Ang II+GW9662, and Ghrelin for 4 wks. In vitro, adult rat cardiac fibroblasts (CFs) were pretreated with or without Ghrelin, Ghrelin+GW9662, or anti-Transforming growth factor (TGF)-β1 antibody and then stimulated with or without Ang II (100 nmol/L) for 24 h. Ang II infusion significantly increased myocardial fibrosis, expression of collagen I, collagen III, and TGF-β1, as well as TGF-β1 downstream proteins p-Smad2, p-Smad3, TRAF6, and p-TAK1 (all p<0.05). Ghrelin attenuated these effects. Similar results were seen in Ang II-stimulated rat cardiac fibroblasts in vitro. In addition, Ghrelin upregulated PPAR-γexpressionin vivoandin vitro, and treatment with GW9662 counteracted the effects of Ghrelin. In conclusion, Ghrelin ameliorated Ang II-induced myocardial fibrosis by upregulating PPAR-γand in turn inhibiting TGF-β1signaling.

scholarly journals Immune Privilege and Eye-Derived T-Regulatory Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Hiroshi Keino ◽  
Shintaro Horie ◽  
Sunao Sugita
Keyword(s):  
Transforming Growth Factor Beta ◽  
T Regulatory Cells ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Cytotoxic T Lymphocyte ◽  
Current Knowledge ◽  
Adaptive Immune Response ◽  
Immune Privilege ◽  
Peripheral Tolerance ◽  
Therapeutic Interventions

Certain cellular components of the eye, such as neural retina, are unable to regenerate and replicate after destructive inflammation. Ocular immune privilege provides the eye with immune protection against intraocular inflammation in order to minimize the risk to vision integrity. The eye and immune system use strategies to maintain the ocular immune privilege by regulating the innate and adaptive immune response, which includes immunological ignorance, peripheral tolerance to eye-derived antigens, and intraocular immunosuppressive microenvironment. In this review, we summarize current knowledge regarding the molecular mechanism responsible for the development and maintenance of ocular immune privilege via regulatory T cells (Tregs), which are generated by the anterior chamber-associated immune deviation (ACAID), and ocular resident cells including corneal endothelial (CE) cells, ocular pigment epithelial (PE) cells, and aqueous humor. Furthermore, we examined the therapeutic potential of Tregs generated by RPE cells that express transforming growth factor beta (TGF-β), cytotoxic T lymphocyte-associated antigen-2 alpha (CTLA-2α), and retinoic acid for autoimmune uveoretinitis and evaluated a new strategy using human RPE-induced Tregs for clinical application in inflammatory ocular disease. We believe that a better understanding of the ocular immune privilege associated with Tregs might offer a new approach with regard to therapeutic interventions for ocular autoimmunity.

scholarly journals NR4A1 modulates inflammation-associated intestinal fibrosis and dampens fibrogenic signaling in myofibroblasts

2021 ◽  
Author(s):  
Vivek Krishna Pulakazhi Venu ◽  
Laurie Alston ◽  
Mircea C Iftinca ◽  
Yi-Cheng Tsai ◽  
Matthew Stephens ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cell Function ◽  
Intestinal Inflammation ◽  
Mesenchymal Cell ◽  
Negative Regulator ◽  
Intestinal Fibrosis ◽  
Luminal Narrowing ◽  
Tgf Β1

Background: Intestinal fibrosis is a common complication of the inflammatory bowel diseases(IBD), contributing to tissue stiffening and luminal narrowing. NR4A1 was previously reported to regulate mesenchymal cell function and dampen fibrogenic signaling. NR4A1 gene variants are associated with IBD risk, and it has been shown to regulate intestinal inflammation. Here, we tested the hypothesis that NR4A1 acts as a negative regulator of intestinal fibrosis through regulating myofibroblast function. Methods: Using the SAMP1/YitFc mouse, we tested whether two pharmacological agents known to enhance NR4A1 signaling: cytosporone B(Csn-B) or 6-mercaptopurine(6-MP); could reduce fibrosis. We also employed the dextran sulphate sodium(DSS) model of colitis and assessed the magnitude of colonic fibrosis in Nr4a1-/- and their wild-type littermates(Nr4a1+/+). Lastly, intestinal myofibroblasts isolated from Nr4a1-/- and Nr4a1+/+ mice or primary human intestinal myofibroblasts were stimulated with transforming growth factor-beta-1(TGF-β1), in the presence or absence of Csn-B or 6-MP, and proliferation and ECM gene expression assessed. Results: Csn-B or 6-MP treatment significantly reduced ileal thickness, collagen and overall ECM content in SAMP1/YitFc mice. This was associated with a reduction in proliferative markers within the mesenchymal compartment. Nr4a1-/- mice exposed to DSS exhibited increased colonic thickening and ECM content. Nr4a1-/- myofibroblasts displayed enhanced TGF-β1-induced proliferation. Furthermore, Csn-B or 6-MP treatment was anti-proliferative in Nr4a1+/+, but not Nr4a1-/- cells. Lastly, activating NR4A1 in human myofibroblasts reduced TGF-β1-induced collagen deposition and fibrosis-related gene expression. Conclusions: Our data suggest that NR4A1 can attenuate fibrotic processes in intestinal myofibroblasts and could provide a valuable clinical target to treat inflammation-associated intestinal fibrosis.

scholarly journals Renoprotective Effect of Platelet-Rich Plasma on Cisplatin-Induced Nephrotoxicity in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Neveen Salem ◽  
Nawal Helmi ◽  
Naglaa Assaf
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Male Rats ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Protective Effects ◽  
Intercellular Adhesion Molecule 1 ◽  
Histopathological Investigation

Platelet-rich plasma (PRP) has grown as an attractive biologic instrument in regenerative medicine for its powerful healing properties. It is considered as a source of growth factors that may induce tissue repairing and improve fibrosis. This product has proven its efficacy in multiple studies, but its effect on cisplatin-induced nephrotoxicity has not yet been elucidated. The present investigation was performed to estimate the protective impact of platelet-rich plasma against cisplatin- (CP-) evoked nephrotoxicity in male rats. Nephrotoxicity was induced in male Wistar rats by right uninephrectomy followed by CP administration. Uninephrectomized rats were assigned into four groups: (1) control group, (2) PRP group, (3) CP group, and (4) CP + PRP group. PRP was administered by subcapsular renal injection. Renal function, inflammatory cytokines, and growth factor level as well as histopathological investigation were carried out. Treatment with PRP attenuated the severity of CP-induced nephrotoxicity as evidenced by suppressed creatinine, blood urea nitrogen (BUN), and N-acetyl glucosaminidase (NAG) levels. Moreover, PRP depressed intercellular adhesion molecule-1 (ICAM-1), kidney injury molecule-1 (KIM-1), caspase-3, and transforming growth factor-beta 1 (TGF-β1) levels, while enhanced the epidermal growth factor (EGF) level. These biochemical results were reinforced by the histopathological investigation, which revealed restoration of normal renal tissue architectures. These findings highlight evidence for the possible protective effects of PRP in a rat model of CP-induced nephrotoxicity, suggesting a new avenue for using PRP to improve the therapeutic index of cisplatin.

scholarly journals Thymoquinone-PLGA-PVA Nanoparticles Ameliorate Bleomycin-Induced Pulmonary Fibrosis in Rats via Regulation of Inflammatory Cytokines and iNOS Signaling

Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 951 ◽  
Author(s):  
Sultan A. M. Saghir ◽  
Naif A. Al-Gabri ◽  
Asmaa F. Khafaga ◽  
Nahla H. El-shaer ◽  
Khaled A. Alhumaidh ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Inflammatory Cytokines ◽  
Transforming Growth Factor Beta ◽  
Water Solubility ◽  
Transforming Growth Factor ◽  
Male Rats ◽  
Control Group ◽  
Albino Rats ◽  
The Third ◽  
Alveolar Septa

Pulmonary fibrosis is considered one of the most chronic interstitial illnesses which are not easily treated. thymoquinone’s (TQ) benefits are still partly problematic due to poor water solubility; therefore, it was loaded onto PLGA-PVA carriers. This study aimed to evaluate the potential effect of TQ-PLGA-PVA nanoparticles (TQ-PLGA-PVA-NPs) on pulmonary fibrosis induced by bleomycin in albino rats. Forty male rats were randomized into four groups. The first group served as the control group; the second and the third groups received bleomycin intratracheally, whereas the third group received TQ-PLGA-PVA-NPs after 4 weeks from bleomycin administration. The fourth group was administrated TQ-PLGA-PVA-NPs alone. The designed nanoparticles appeared around 20 nm size (10–30 nm), had a spherical shape, and had 80% encapsulation efficiency. The histological examination of rats simultaneously treated with TQ-PLGA-PVA-NPs and bleomycin revealed reduction in the thickness of the alveolar septa and improvement of the other lung structures, with the presence of lymphocytes admixed with exfoliated epithelium in a few lumina remaining. Ultrastructural findings revealed marked collagenolysis and the release of nanoparticles from ruptured pneumocytes within the alveolar septa after 14 days from TQ-PLGA-PVA-NPs administration. Very active pneumocyte types II were seen in the TQ-PLGA-PVANP group. Additionally, immunohistochemical expression of inducible nitric oxide (iNOS) and estimation of inflammatory cytokines in lung tissues including interleukin 10 (IL 10) and transforming growth factor-beta (TGF-β1) confirmed the antioxidant and anti-inflammatory effects of TQ-PLGA-PVANPs. The study concluded that TQ-PLGA-PVA-NPs could attenuate the bleomycin-induced pulmonary fibrosis, through the inhibition of lung inflammation and the suppression of bleomycin- induced oxidative stress.

scholarly journals Dietary Sodium Restriction Reduces Arterial Stiffness, Vascular TGF-β-Dependent Fibrosis and Marinobufagenin in Young Normotensive Rats

2018 ◽  
Vol 19 (10) ◽  
pp. 3168 ◽  
Author(s):  
Yulia Grigorova ◽  
Wen Wei ◽  
Natalia Petrashevskaya ◽  
Valentina Zernetkina ◽  
Ondrej Juhasz ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Aortic Stiffness ◽  
Aortic Wall ◽  
Transforming Growth Factor ◽  
Dietary Sodium ◽  
Sprague Dawley ◽  
Dietary Salt ◽  
Salt Reduction ◽  
Salt Consumption ◽  
Salt Sensitive Hypertension

High salt (HS) intake stimulates the production of marinobufagenin (MBG), an endogenous steroidal Na/K-ATPase ligand, which activates profibrotic signaling. HS is accompanied by a blood pressure (BP) increase in salt-sensitive hypertension, but not in normotensive animals. Here, we investigated whether HS stimulates MBG production and activates transforming growth factor-beta (TGF-β) profibrotic signaling in young normotensive rats, and whether these changes can be reversed by reducing salt to a normal salt (NS) level. Three-month old male Sprague–Dawley rats received NS for 4 and 8 weeks (0.5% NaCl; NS4 and NS8), or HS for 4 and 8 weeks (4% NaCl; HS4 and HS8), or HS for 4 weeks followed by NS for 4 weeks (HS4/NS4), n = 8/group. Systolic BP (SBP), pulse wave velocity (PWV), MBG excretion, aortic collagen 1α2, collagen 4α1 and TGF-β, Smad2, Smad3, Fli-1 mRNA, and total collagen abundance were measured at baseline (BL), and on weeks 4 and 8. Statistical analysis was performed using one-way ANOVA. SBP was not affected by HS (125 ± 5 and 126 ± 6 vs. 128 ± 7 mmHg, HS4 and HS8 vs. BL, p > 0.05). HS increased MBG (164 ± 19 vs. 103 ± 19 pmol/24 h/kg, HS4 vs. BL, p < 0.05) and PWV (3.7 ± 0.2 vs. 2.7 ± 0.2 m/s, HS4 vs. NS4, p < 0.05). HS8 was associated with a further increase in MBG and PWV, with an increase in aortic Col1a2 80%), Col4a1 (50%), Tgfb1 (30%), Smad2 (30%) and Smad3 (45%) mRNAs, and aortic wall collagen (180%) vs. NS8 (all p < 0.05). NS following HS downregulated HS-induced factors: in HS4/NS4, the MBG level was 91 ± 12 pmol/24 h/kg (twofold lower than HS8, p < 0.01), PWV was 3.7 ± 0.3 vs. 4.7 ± 0.2 m/s (HS4/NS4 vs. HS8, p < 0.05), aortic wall Tgfb1, Col1a2, Col4a1, Smad2, Smad3 mRNAs, and collagen abundance were reversed by salt reduction to the BL levels (p < 0.05). HS was associated with an activation of TGF-β signaling, aortic fibrosis and aortic stiffness accompanied by an MBG increase in the absence of SBP changes in young normotensive rats. The reduction of dietary salt following HS decreased MBG, PWV, aortic wall collagen and TGF-β. Thus, HS-induced aortic stiffness in normotensive animals occurred in the context of elevated MBG, which may activate SMAD-dependent TGF-β pro-fibrotic signaling. This data suggests that a decrease in salt consumption could help to restore aortic elasticity and diminish the risk of cardiovascular disease by reducing the production of the pro-fibrotic factor MBG.

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