scholarly journals Nephroprotective Effect of Pentoxyphylline Through Improvement in the Expression of TGF-beta1, Collagen Type-1, and Renal Interstitial Fibrosis in Swiss Strain Mice After Being Induced by Doxorubicin

2010 ◽  
Vol 2 (2) ◽  
pp. 46
Author(s):  
Bambang Purwanto ◽  
A Guntur Hermawan
Keyword(s):  
Collagen Type ◽  
Interstitial Fibrosis ◽  
Collagen Type I ◽  
Type I ◽  
Renal Interstitial Fibrosis ◽  
Collagen Type 1 ◽  
Nephroprotective Effect ◽  
Tgf Β1 ◽  
Swiss Strain

BACKGROUND: Use of doxorubicin (DXR) in the treatment of cancer has been increasing along with the increase in cancer morbidity. Nephrotoxic effects of DXR are still a problem. Pentoxyphylline (PTX) as an electron-donor material can be nephroprotective, so the combination of DXR and PTX might reduce the nephrotoxic effects of DXR. The aim of this study was to prove the nephroprotective effect of PTX and DXR nephrotoxicity through the improvement of TGF-β1, collage type-1, and renal interstitial fibrosis.METHODS: Twenty-four males Swiss strain mice, divided into three groups namely Control (C) injected with NaCl 0.9%; DXR induced nephrotoxicity (D); and effect of PTX on D (P/D) by intraperitoneally, respectively, each group consisted of 8 mice. Injections were given once a week for three consecutive weeks. At 8th week post-treatment, all eight mice of each group were sacrificed. Examination of TGF-β1 and collagen type-I expression was done by immunohistochemistry with monoclonal antibody. Renal interstitial fibrosis examination was done by a histopathologist, using Verheoff van Giesen staining. The statistic analysis was carried out using one-way ANOVA.RESULTS: TGF-β1 expression increased from C to D and subsequently decreased in P/D (4.50±3.89 vs. 177.88±68.78 vs. 36.88±9.51). Collagen type-I expression increased from C to D and subsequently decreased in P/D (12.00±14.32 vs. 186.25±125.62 vs. 36.00±29.14). Renal interstitial fibrosis expression increased from C to D and subsequently decreased in P/D (16.75±6.14 vs. 85.00±7.33 vs. 60.50±11.40). The expression of TGF-β1, collagen type-1, and renal interstitial fibrosis were higher significantly in D group as compared to C group (p<0,001). The expression of TGF-β1, collagen type-1, and renal interstitial fibrosis were lower significantly in P/D group as compared to D group (p<0.005).CONCLUSIONS: PTX was proved to be nephroprotector inducing by DXR.KEYWORDS: PTX, nephroprotector, TGF-β1, collagen type-I, renal interstitial fibrosis

scholarly journals Microvessel vascular smooth muscle cells contribute to collagen type I deposition through ERK1/2 MAP kinase, αvβ3-integrin, and TGF-β1 in response to ANG II and high glucose

2008 ◽  
Vol 295 (1) ◽  
pp. H69-H76 ◽  
Author(s):  
Souad Belmadani ◽  
Mourad Zerfaoui ◽  
Hamid A. Boulares ◽  
Desiree I. Palen ◽  
Khalid Matrougui
Keyword(s):  
Map Kinase ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Ang Ii ◽  
Diabetic Mice ◽  
Smad2 Phosphorylation ◽  
Collagen Type 1 ◽  
Tgf Β1

This study determines that vascular smooth muscle cell (VSMC) signaling through extracellular signal-regulated kinase (ERK) 1/2-mitogen-activated protein (MAP) kinase, αvβ3-integrin, and transforming growth factor (TGF)-β1 dictates collagen type I network induction in mesenteric resistance arteries (MRA) from Type 1 diabetic (streptozotocin) or hypertensive (HT; ANG II) mice. Isolated MRA were subjected to a pressure-passive-diameter relationship. To delineate cell types and mechanisms, cultured VSMC were prepared from MRA and stimulated with ANG II (100 nM) and high glucose (HG, 22 mM). Pressure-passive-diameter relationship reduction was associated with increased collagen type I deposition in MRA from HT and diabetic mice compared with control. Treatment of HT and diabetic mice with neutralizing TGF-β1 antibody reduced MRA stiffness and collagen type I deposition. Cultured VSMC stimulated with HG or ANG II for 5 min increased ERK1/2-MAP kinase phosphorylation, whereas a 48-h stimulation induced latent TGF-β1, αvβ3-integrin, and collagen type 1 release in the conditioned media. TGF-β1 bioactivity and Smad2 phosphorylation were αvβ3-integrin-dependent, since β3-integrin antibody and αvβ3-integrin inhibitor (SB-223245, 10 μM) significantly prevented TGF-β1 bioactivity and Smad2 phosphorylation. Pretreatment of VSMC with ERK1/2-MAP kinase inhibitor (U-0126, 1 μM) reduced αvβ3-integrin, TGF-β1, and collagen type 1 content. Additionally, αvβ3-integrin antibody, SB-223245, TGF-β1-small-intefering RNA (siRNA), and Smad2-siRNA (40 nM) prevented collagen type I network formation in response to ANG II and HG. Together, these data provide evidence that resistance artery fibrosis in Type 1 diabetes and hypertension is a consequence of abnormal collagen type I release by VSMC and involves ERK1/2, αvβ3-integrin, and TGF-β1 signaling. This pathway could be a potential target for overcoming small artery complications in diabetes and hypertension.

scholarly journals Precision-Cut Kidney Slices as a Tool to Understand the Dynamics of Extracellular Matrix Remodeling in Renal Fibrosis

2016 ◽  
Vol 11 ◽  
pp. BMI.S38439 ◽  
Author(s):  
Federica Genovese ◽  
Zsolt S. Kàrpàti ◽  
Signe H. Nielsen ◽  
Morten A. Karsdal
Keyword(s):  
Extracellular Matrix ◽  
Collagen Type ◽  
Interstitial Fibrosis ◽  
Ex Vivo ◽  
Collagen Type I ◽  
Extracellular Matrix Remodeling ◽  
Type I ◽  
Matrix Remodeling ◽  
Renal Interstitial Fibrosis ◽  
Ex Vivo Model

The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) surgery of the right ureter. The left kidney (contralateral) was used as internal control. Six rats were sham operated and used as the control group. Rats were terminated two weeks after the surgery; the kidneys were excised and precision-cut kidney slices (PCKSs) were cultured for five days in serum-free medium. Markers of collagen type I formation (P1NP), collagen type I and III degradation (C1M and C3M), and α-smooth muscle actin (αSMA) were measured in the PCKS supernatants by enzyme-linked immunosorbent assay. P1NP, C1M, C3M, and α-SMA were increased up to 2- to 13-fold in supernatants of tissue slices from the UUO-ligated kidneys compared with the contralateral kidneys ( P < 0.001) and with the kidneys of sham-operated animals ( P < 0.0001). The markers could also reflect the level of fibrosis in different animals. The UUO PCKS ex vivo model provides a valuable translational tool for investigating the extracellular matrix remodeling associated with renal interstitial fibrosis.

Membranes of Chitosan and Collagen-Type 1 for Biomineralization/Ostheogenesis

2013 ◽  
Vol 587 ◽  
pp. 222-226
Author(s):  
Ricardo B. Pacheco ◽  
Marina Salvarani Tonoli ◽  
Marisa Masumi Beppu
Keyword(s):  
Collagen Type ◽  
Collagen Type I ◽  
Calcium Deposition ◽  
Collagen Membrane ◽  
Type I ◽  
Chitosan Membranes ◽  
Collagen Membranes ◽  
Collagen Type 1

The main objective of this work was to produce membranes of chitosan and collagen type I and check their ability to undergo “in vitro” calcification. The membranes of chitosan-collagen blends were characterized by TGA, infra-red spectroscopy and DSC. Samples of dense and porous membranes were immersed in solution SBF (Simulated Body Fluid) in order to verify their “in vitro” calcification. The membranes were observed by SEM. The production of chitosan-collagen membranes is possible, in dense and porous versions. We can conclude that the blend is less resistant to high temperatures, in comparison to pristine chitosan membranes shown in literature. Through the initial assays of calcification, we observe that it is possible to induce the calcium deposition on a chitosan-collagen membrane, as seen by SEM. Microscopy of fracture surfaces showed fibril structures, probably formed by collagen.

scholarly journals The NF-kB and Collagen Type 1 Expression in Dental Pulp after Treated Calcium Hydroxide Combined with Propolis

2021 ◽  
Author(s):  
Nirawati Pribadi ◽  
Dwita Budiarti ◽  
Hendy Jaya Kurniawan ◽  
Ira Widjiastuti
Keyword(s):  
Calcium Hydroxide ◽  
Dental Pulp ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Treatment Groups ◽  
Pulp Inflammation ◽  
Time Frames ◽  
Collagen Type 1

Abstract Objective To analyze the expression of nuclear factor kappa B (NF-kB) and collagen type 1 on dental pulp after a treated combination of calcium hydroxide and propolis. Materials and Methods The first maxillary molars of 30 rats were mechanically perforated. Teeth were divided into three groups of 10 for two separate extraction time frames, giving a total of 60 rats. The control groups were treated with Cention, the second treatment groups were treated with calcium hydroxide, and the third treatment groups were treated with a combination of calcium hydroxide and propolis. Final restoration was done with Cention. The teeth were extracted on days 7 and 14, and the expression of NF-kB and collagen type I was analyzed using immunohistochemistry. Results There is lowest NF-kB expression and highest collagen type 1 expression on dental pulp after treated with a combination of calcium hydroxide and propolis on days 7 and 14 (p < 0.05). Conclusion The combination of calcium hydroxide and propolis inhibits pulp inflammation and stimulates regeneration through decreasing the NF-kB expression and increasing collagen type 1.

scholarly journals Salacia chinensis L. Stem Extract Exerts Antifibrotic Effects on Human Hepatic Stellate Cells through the Inhibition of the TGF-β1-Induced SMAD2/3 Signaling Pathway

2019 ◽  
Vol 20 (24) ◽  
pp. 6314 ◽  
Author(s):  
Mattareeyapar Phaosri ◽  
Salinee Jantrapirom ◽  
Mingkwan Na Takuathung ◽  
Noppamas Soonthornchareonnon ◽  
Seewaboon Sireeratawong ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Collagen Type ◽  
Stellate Cell ◽  
Scientific Evidence ◽  
Collagen Type I ◽  
Type I ◽  
Noticeable Increase ◽  
Stem Extract ◽  
Collagen Type 1 ◽  
Tgf Β1

Salacia chinensis L. (SC) stems have been used as an ingredient in Thai traditional medicine for treating patients with hepatic fibrosis and liver cirrhosis. However, there is no scientific evidence supporting the antifibrotic effects of SC extract. Therefore, this study aimed to determine the antifibrotic activity of SC stem extract in human hepatic stellate cell-line called LX-2. We found that upon TGF-β1 stimulation, LX-2 cells transformed to a myofibroblast-like phenotype with a noticeable increase in α-SMA and collagen type I production. Interestingly, cells treated with SC extract significantly suppressed α-SMA and collagen type I production and reversed the myofibroblast-like characteristics back to normal. Additionally, TGF-β1 also influenced the development of fibrogenesis by upregulation of MMP-2, TIMP-1, and TIMP-2 and related cellular signaling, such as pSmad2/3, pErk1/2, and pJNK. Surprisingly, SC possesses antifibrotic activity through the suppression of TGF-β1-mediated production of collagen type 1, α-SMA, and the phosphorylation status of Smad2/3, Erk1/2, and JNK. Taken together, the present study provides accumulated information demonstrating the antifibrotic effects of SC stem extract and revealing its potential for development for hepatic fibrosis patients.

scholarly journals Mesenchymal Stem Cells Ameliorate Interstitial Fibrosis in Adenine-induced Nephropathy Based on Renal Proteomics

2020 ◽  
Author(s):  
Huajun Tang ◽  
Peiyue Zhang ◽  
Lianlin Zeng ◽  
Yu Zhao ◽  
Libo Xie ◽  
...  
Keyword(s):  
Western Blot ◽  
Therapeutic Target ◽  
Bioinformatics Analysis ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Histopathological Change ◽  
Collagen Type I ◽  
Tubulointerstitial Fibrosis ◽  
Type I ◽  
Tgf Β1

Abstract Background: Tubulointerstitial fibrosis (TIF) is one of the main pathological features of various progressive renal damages and chronic kidney diseases. Mesenchymal stromal cells (MSCs) have been verified with significant improvement in the therapy of fibrosis diseases, but the mechanism is still unclear. We attempted to explore the new mechanism and therapeutic target of MSCs against renal fibrosis based on renal proteomics.Methods: TIF model was induced by adenine gavage. Bone marrow derived MSCs was injected by tail vein after modeling. Fibrosis biomarkers or extracellular matrix proteins and histopathological change were assessed by Masson staining, Sirius red staining, immunohistochemistry, and western blot. Renal proteomics was analyzed using iTRAQ-based mass spectrometry.Results: MSCs treatment clearly decreased the expression of α-SMA, collagen type I, II, III, TGF-β1, p-Smad2/3, IL-6, IL-1β, and TNFα compared with model rats, while p38 MAPK increased. 6,213 proteins were identified, but only 40 proteins exhibited significant differences (30 upregulated, 10 downregulated) compared MSCs group with the model group. Bioinformatics analysis revealed that these proteins play important roles in the proliferation, inflammatory and immune responses, apoptosis, phagosome, etc. According to literatures and bioinformatics analysis, the most markedly downregulated protein, galectin3, was further assessed by quantitative PCR and western blot in renal tissues. Galectin3 levels were downregulated in adenine-induced renal tissues and TGF-β1 induced tubular epithelial cells and interstitial fibroblasts in consistent with iTRAQ after MSCs treatment.Conclusion: The founds suggest that galectin3 maybe involves in the antifibrotic mechanisms of MSCs therapy for tubulointerstitial fibrosis as well as a possible therapeutic target.

Abstract 48: Age-associated Imbalance of Vasorin/TGF-β1 Signaling in VSMC Facilitates Collagen Production

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Mingyi Wang ◽  
Gianfranco Pintus ◽  
Roberta Giordo ◽  
Jing Zhang ◽  
Liqun Jiang ◽  
...  
Keyword(s):  
Arterial Wall ◽  
Collagen Type ◽  
Collagen Type I ◽  
In Vivo Studies ◽  
Physical Interaction ◽  
Type I ◽  
Ang Ii ◽  
Collagen Production ◽  
At1 Antagonist ◽  
Tgf Β1

Collagen deposition, a hallmark of arterial aging that resembles post-injury arterial restenosis, is perpetrated by angiotensin II (Ang II) signaling in arterial wall. Collagen aggregation at sites of arterial injury is regulated by the coordinated signaling of pro-fibrotic TGF-β1 and anti-fibrotic vasorin within VSMCs. The Ang II/TGF-β1/vasorin signaling relationship within VSMCs with aging, however, remains unknown. In vivo studies in old vs. young FXBN rats show that aortic transcription and translation of vasorin markedly decrease with aging. In vitro studies in VSMCs isolated from old vs. young aortae. Ang II-associated reduction of vasorin protein abundance in young VSMCs and age-associated changes in vasorin protein levels are reversed by the AT1 antagonist, Losartan (Los) (Figure). Dual immunolabeling and co-immunoprecipitation demonstrate that the co-incidence and physical interaction of vasorin and TGF-β1 within VSMCs are significantly decreased with aging. Importantly, exposure of young VSMCs to Ang II that increases p-SMAD2/3 and collagen type I production, mimicking old cells, and this effect is abolished or substantially mitigated by Los treatment, overexpression of ectopic vasorin, or exogenous recombinant human-vasorin protein. In contrast, exposure of old VSMCs to Los decreases p-SMAD2/3 and collagen type I production.Thus, an imbalance of the Ang II/TGF-β1/vasorin signaling cascade, a feature of the aged arterial wall, enhances the collagen production by VSMCs. Maintaining this signaling balance is a novel measure to retard adverse extracellular matrix remodeling, a determinant of arterial stiffening with aging. (MW and GP co-first authors)

Abstract 96: Simvastatin Prevents TGF-β1-induced SMAD2/3 Phosphorylation Involved in Ventricular Fibrosis: Role of Protein Phosphatases

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Farhan Rizvi ◽  
Ramail Siddiqui ◽  
Alessandra DeFranco ◽  
Alisher Holmuhamedov ◽  
Hao Xu ◽  
...  
Keyword(s):  
Western Blot ◽  
Cardiac Fibrosis ◽  
Collagen Type ◽  
Protein Phosphatases ◽  
Collagen Type I ◽  
Type I ◽  
Smad Protein ◽  
The Media ◽  
Ventricular Fibrosis ◽  
Tgf Β1

Background: Ventricular fibrosis leads to progressive cardiac dysfunction and heart failure (HF). Statins are reported to reduce cardiac fibrosis through the cholesterol-independent pathway, but mechanisms remain elusive. We hypothesize simvastatin reduced TGF-β1-induced ventricular fibrosis through activation of SMAD protein phosphatase Mg 2+ /Mn 2+ -1A (PPM1A), -2A (PP2A). Methods: In the absence and presence of TGF-β1 (5ng) with or without simvastatin (1μM), the rate of fibroblast proliferation (doubling time), myofibroblast differentiation (ICC), α-SMA mRNA (RT-PCR) and protein expression (Western blot) and the release of collagen synthesis markers, pro-collagen type I C-terminal peptide (PICP) and pro-collagen type III N-terminal peptide (PIIINP), in the media (ELISA) were determined along with protein interaction between SMAD2/3 and PPM1A or PP2A (Co-IP) and SMAD2/3 phosphorylation (Western blot). Results: Simvastatin reduced the effect of TGF-β1 on hVF proliferation by 47% (50000 to 26500), p<0.01; myofibroblast differentiated population from 48% (avg 48/100) to 11% (avg 11/100), p<0.01; expression of α-SMA mRNA by 76%, p<0.01; and protein by 60%, p<0.05. Simvastatin also decreased release of PICP by 66%, p<0.01, and PIIINP by 83%, p<0.01, into the media. Time-dependent increases in SMAD2/3 phosphorylation were reduced by simvastatin through activation of protein phosphatases PPM1A and PP2A by interacting with SMAD2/3. Conclusion: Involvement of PPM1A and PP2A in the anti-fibrotic effect of simvastatin reveals novel signaling mediators that may be selectively targeted for prevention of myocardial injury-induced ventricular fibrosis and HF.

scholarly journals Glycolysis inhibitors suppress renal interstitial fibrosis via divergent effects on fibroblasts and tubular cells

2019 ◽  
Vol 316 (6) ◽  
pp. F1162-F1172 ◽  
Author(s):  
Qingqing Wei ◽  
Jennifer Su ◽  
Guie Dong ◽  
Ming Zhang ◽  
Yuqing Huo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Pathological Feature ◽  
Renal Interstitial Fibrosis ◽  
Tubular Cells ◽  
Glycolysis Inhibitors

Renal interstitial fibrosis is a common pathological feature of chronic kidney disease that may involve changes of metabolism in kidney cells. In the present study, we first showed that blockade of glycolysis with either dichloroacetate (DCA) or shikonin to target different glycolytic enzymes reduced renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO). Both inhibitors evidently suppressed the induction of fibronectin and collagen type I in obstructed kidneys, with DCA also showing inhibitory effects on collagen type IV and α-smooth muscle actin (α-SMA). Histological examination also confirmed less collagen deposition in DCA-treated kidneys. Both DCA and shikonin significantly inhibited renal tubular apoptosis but not interstitial apoptosis in UUO. Macrophage infiltration after UUO injury was also suppressed. Shikonin, but not DCA, caused obvious animal weight loss during UUO. To determine whether shikonin and DCA worked on tubular cells and/or fibroblasts, we tested their effects on cultured renal proximal tubular BUMPT cells and renal NRK-49F fibroblasts during hypoxia or transforming growth factor-β1 treatment. Although both inhibitors reduced fibronectin and α-SMA production in NRK-49F cells during hypoxia or transforming growth factor-β1 treatment, they did not suppress fibronectin and α-SMA expression in BUMPT cells. Altogether, these results demonstrate the inhibitory effect of glycolysis inhibitors on renal interstitial fibrosis. In this regard, DCA is more potent for fibrosis inhibition and less toxic to animals than shikonin.

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