Abstract 372: Regulation of Ski and Scleraxis in the Infarcted Rat Heart

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Krista L Filomeno ◽  
Sunil G Rattan ◽  
Sheri Bage ◽  
Matthew Zeglinski ◽  
Michael P Czubryt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Mrna Expression ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Scar Tissue ◽  
Sprague Dawley ◽  
Scar Area ◽  
Tgf Β1

Introduction: Coronary heart disease is causal to myocardial infarction (MI) and cardiac fibrosis. Upon ischemic myocardial injury, resident cardiac fibroblasts phenoconvert to myofibroblasts and synthesize large amounts of fibrillar collagens to produce scar tissue. Although the myofibroblast numbers are reduced in the infarct scar following the completion of wound healing, a sub-population of cells persist in the wounded area, leading to maladaptive chronic remodeling of the scar area and eventually the non-infarcted myocardium. Ski has been identified as a repressor of the TGF-β1 signaling pathway, attenuating the myofibroblast phenotype and its functional properties. Scleraxis has been implicated in canonical TGF-β1 signaling to promote collagen1α2 expression. We investigated how Ski and Scleraxis contribute to physiological and pathological wound healing in vivo. Methods: The study was carried out using 64 male Sprague-Dawley rats. The left anterior descending (LAD) coronary artery was ligated to induce a myocardial infarction. Control (sham) operated animals underwent surgery without ligation of the LAD artery. Animals were sacrificed at 2, 4, and 8 weeks post-MI and tissue collected for Western blot and qPCR studies. Results: Scleraxis mRNA expression remained at baseline at 2 and 8 weeks post-MI, but was significantly increased 4 weeks post-MI. Scleraxis protein expression was down-regulated within the scar area of infarcted hearts when compared to control samples 2 and 4 weeks post-MI. Ski mRNA expression was up-regulated within the scar area of infarcted hearts 2, 4 and 8 weeks after infarction. Conclusions: Scleraxis protein is down-regulated in myofibroblasts of the infarct scar in the chronic stages of myocardial infarction, corresponding to the maturation of the scar. At these stages of wound healing, we have previously published that Ski is up-regulated in the cytosol of these same cells. We suggest reciprocal feedback in the expression of these two proteins exists in myofibroblasts in the infarct scar. We hope to learn more about the Ski/Scleraxis feedback loop in pathological wound healing to identify novel therapeutic targets.

scholarly journals Long Non-Coding RNA 554 Promotes Cardiac Fibrosis via TGF-β1 Pathway in Mice Following Myocardial Infarction

2020 ◽  
Vol 11 ◽  
Author(s):  
Bihui Luo ◽  
Zhiyu He ◽  
Shijun Huang ◽  
Jinping Wang ◽  
Dunzheng Han ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Non Coding Rna ◽  
Novel Target ◽  
And Function ◽  
Tgf Β1

Rationale: Cardiac fibrosis is observed in nearly every form of myocardial disease. Long non-coding RNAs (lncRNAs) have been shown to play an important role in cardiac fibrosis, but the detailed molecular mechanism remains unknown.Object: We aimed at characterizing lncRNA 554 expression in murine cardiac fibroblasts (CFs) after myocardial infarction (MI) to identify CF-enriched lncRNA and investigate its function and contribution to cardiac fibrosis and function.Methods and Results: In this study, we identified lncRNA NONMMUT022554 (lncRNA 554) as a regulator of MI-induced cardiac fibrosis. We found that lncRNA 554 was significantly up-regulated in the mouse hearts following MI. Further study showed that lncRNA 554 was predominantly expressed in cardiac fibroblasts, indicating a potential role of lncRNA 554 in cardiac fibrosis. In vitro knockdown of lncRNA 554 by siRNA suppressed fibroblasts migration and expression of extracellular matrix (ECM); while overexpression of lncRNA 554 promoted expression of ECM genes. Consistently, lentivirus mediated in vivo knockdown of lncRNA 554 could inhibit cardiac fibrosis and improve cardiac function in mouse model of MI. More importantly, TGF-β1 inhibitor (TEW-7197) could reverse the pro-fibrotic function of lncRNA 554 in CFs. This suggests that the effects of lncRNA 554 on cardiac fibrosis is TGF-β1 dependent.Conclusion: Collectively, our study illustrated the role of lncRNA 554 in cardiac fibrosis, suggested that lncRNA 554 might be a novel target for cardiac fibrosis.

scholarly journals Cardiomyocyte Derived miR-328 Promotes Cardiac Fibrosis by Paracrinely Regulating Adjacent Fibroblasts

2018 ◽  
Vol 46 (4) ◽  
pp. 1555-1565 ◽  
Author(s):  
Dandan Zhao ◽  
Cui Li ◽  
He Yan ◽  
Tianyu Li ◽  
Ming Qian ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Left Coronary Artery ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Collagen Deposition ◽  
Paracrine Signaling ◽  
Potential Therapeutic Target ◽  
Transmission Electron ◽  
Elevated Expression ◽  
Tgf Β1

Background/Aims: In our previous study, we demonstrated that elevated expression of miR-328 is a potent determinant of cardiac fibrosis during myocardial infarction (MI). In the present study, histological examination revealed progressive fibrosis in transgenic mice overexpressing cardiomyocyte-specific miR-328. This study investigated whether the transfer of miR-328 from cardiomyocytes (CMs) to cardiac fibroblasts (CFs) in a paracrine manner contributes to myocardial fibrosis. Methods: Myocardial infarction was established by the occlusion of the left coronary artery. Masson’s trichrome staining and collagen assays were used to evaluate the progression of fibrosis. The vesicles and translocation of miR-328 in a co-culture assay system were respectively observed using transmission electron microscopy (TEM) and immunofluorescence staining (IF). Real-time PCR was employed to detect the level of miR-328, Col1α1 and Col3α1. The protein expression of Col1α1, TGF-βRIII, p-smad2/3 (phosphorylated-smad2/3) and TGF-β1 were probed using western blot analysis. Results: Cardiomyocyte-specific miR-328 overexpressing transgenic (TG) mice showed enhanced collagen deposition and provoked cardiac fibrosis by the activation of the TGF-β1 pathway, and this effect was abrogated after knockdown of endogenous miR-328 in mice. Correspondingly, the expression of miR-328 was increased in CFs co-cultured with CMs transfected with miR-328 mimics, likely in a paracrine manner. The cardiomyocyte-mediated augmentation of miR-328 contributes to fibrogenesis in CFs, and this pro-fibrotic effect was reversed after the transfection of miR-328 inhibitor in CFs. Conclusion: A novel molecular mechanism for miR-328 derived from CMs as a paracrine signaling mediator of cardiac fibrogenesis further demonstrates that miR-328 is a potential therapeutic target.

Abstract 98: Profiling GPCR Expression in Cardiac Fibroblasts and Myofibroblasts

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Krishna Sriram ◽  
Nakon Aroonsakool ◽  
Alexander Michkov ◽  
Paul Insel
Keyword(s):  
Mrna Expression ◽  
G Protein ◽  
Drug Targets ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Ex Vivo ◽  
Cardiac Fibroblasts ◽  
Expression Profiles ◽  
Protein Detection

G-protein coupled receptors (GPCRs) are the largest class of cell surface receptors, serving as drug targets, at least in part, due to their diversity, selectivity in tissue expression and ability to regulate a wide variety of cellular functions. We hypothesized that cardiac fibroblasts (CFs) and pro-fibrotic myofibroblasts (myoFs) may express GPCRs that will regulate their activity and will identify previously unappreciated GPCRs as potential therapeutic targets for cardiac fibrosis. To test this hypothesis, we profiled non-chemosensory GPCR mRNA expression by using qPCR-based GPCR arrays in studies of CFs isolated from ventricular tissue of rats, mice and humans. Particular attention was paid to assessing cells at low passage (1-3) and grown on substrates that mimic the stiffness of cardiac tissue in-vivo. MyoFs were obtained by treating CFs ex-vivo with TGFβ, and from CFs that spontaneously transformed to MyoFs by growth on hard tissue culture substrates.We find that CFs from humans, rats and mice express ~120 GPCRs and that a majority of GPCRs (>75%), especially highly expressed GPCRs, are detected in human, rats and/or mice CFs; ~40% of highly expressed GPCRs are orphan receptors (without known physiologic agonists). Of GPCRs with known G-protein linkages, Gi-coupled receptors are most numerous, followed by Gq-, Gs- and G12/13-coupled GPCRs. GPCR expression profiles of rat atrial and ventricular CFs are highly similar in terms of both identity and level of expression. By contrast, GPCR expression in cardiac myocytes (CMs) differs significantly from CFs: most highly expressed receptors in CFs are undetected or much lower expressed in CMs. Several GPCRs detected in MyoFs have reduced expression vs CFs but a subset of GPCRs have higher expression in MyoFs. Validation of mRNA expression via protein detection as well as functional assays helps confirm the presence of a large number of the GPCRs. Conclusions: CFs and MyoFs from rodents and humans express ~120 GPCRs, including many orphan GPCRs. Atrial and ventricular CFs have similar GPCR profiles but ones that differ from that of CMs. CFs and MyoFs show differences in the number and nature of GPCRs expressed. We hypothesize that GPCRs higher expressed in MyoFs may contribute to their pro-fibrotic phenotype.

scholarly journals Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7

2017 ◽  
Vol 42 (6) ◽  
pp. 2207-2219 ◽  
Author(s):  
Jinxia Yuan ◽  
Hongtao Chen ◽  
Dawei Ge ◽  
Yu Xu ◽  
Haihua Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Fibrosis ◽  
Cardiac Fibrosis ◽  
Critical Role ◽  
Luciferase Reporter Assay ◽  
In Vivo Study ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Tgf Β1

Background/Aims: Cardiac fibrosis after myocardial infarction (MI) has been identified as an important factor in the deterioration of heart function. Previous studies have demonstrated that miR-21 plays an important role in various pathophysiological processes in the heart. However, the role of miR-21 in fibrosis regulation after MI remains unclear. Methods: To induce cardiac infarction, the left anterior descending coronary artery was permanently ligated of mice. First, we explored the expression of miR-21 in the infarcted zone in mice model of MI via RT-qPCR. Next, we examined the effects of TGF-β1 on miR-21 expression in cardiac fibroblasts (CFs). Then, CFs were infected with miR-21 mimics or miR-21 inhibitors to investigate the effects of miR-21 on the process of CFs activation in vitro. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-21. At last, in-vivo study was done to confirm MiR-21 regulated myocardial fibrosis after MI in mice. Results: MiR-21 was up-regulated in the infarcted zone after MI in vivo. TGF-β1 treatment increased miR-21 expression in CFs. Overexpression of miR-21 promoted the effects of TGF-β1-induced activation of CFs, evidenced by increased expression of Col-1, α-SMA and F-actin, whereas inhibition of miR-21 attenuated the process of fibrosis. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that Smad7 is a direct target of miR-21. In addition, in-vivo study revealed that MiR-21 regulated myocardial fibrosis after MI in mice. Conclusion: These findings suggested that miR-21 has a critical role in CF activation and cardiac fibrosis after MI through via TGF-β/Smad7 signaling pathway. Thus, miR-21 promises to be a potential therapy in treatment of cardiac fibrosis after MI.

scholarly journals P300/CBP-Associated Factor Activates Cardiac Fibroblasts by SMAD2 Acetylation

2021 ◽  
Vol 22 (18) ◽  
pp. 9944
Author(s):  
Yongwoon Lim ◽  
Anna Jeong ◽  
Duk-Hwa Kwon ◽  
Yeong-Un Lee ◽  
Young-Kook Kim ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Heart Diseases ◽  
High Dose ◽  
Mouse Heart ◽  
Associated Factor ◽  
Tgf Β1

Various heart diseases cause cardiac remodeling, which in turn leads to ineffective contraction. Although it is an adaptive response to injury, cardiac fibrosis contributes to this remodeling, for which the reactivation of quiescent myofibroblasts is a key feature. In the present study, we investigated the role of the p300/CBP-associated factor (PCAF), a histone acetyltransferase, in the activation of cardiac fibroblasts. An intraperitoneal (i.p.) injection of a high dose (160 mg/kg) of isoproterenol (ISP) induced cardiac fibrosis and reduced the amount of the PCAF in cardiac fibroblasts in the mouse heart. However, the PCAF activity was significantly increased in cardiac fibroblasts, but not in cardiomyocytes, obtained from ISP-administered mice. An in vitro study using human cardiac fibroblast cells recapitulated the in vivo results; an treatment with transforming growth factor-β1 (TGF-β1) reduced the PCAF, whereas it activated the PCAF in the fibroblasts. PCAF siRNA attenuated the TGF-β1-induced increase in and translocation of fibrosis marker proteins. PCAF siRNA blocked TGF-β1-mediated gel contraction and cell migration. The PCAF directly interacted with and acetylated mothers against decapentaplegic homolog 2 (SMAD2). PCAF siRNA prevented TGF-β1-induced phosphorylation and the nuclear localization of SMAD2. These results suggest that the increase in PCAF activity during cardiac fibrosis may participate in SMAD2 acetylation and thereby in its activation.

Abstract 17179: Uremic Toxins Contribute to Cardiac Fibrosis after Myocardial Infarction: Role of MicroRNAs

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Indrajeet Rana ◽  
Andrew Kompa ◽  
Joanna Skommer ◽  
Suree Lekawanvijit ◽  
Darren J Kelly ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Cardiac Fibrosis ◽  
Uremic Toxins ◽  
Coronary Artery Ligation ◽  
Uremic Toxin ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Tgf Β1

Introduction: A decline in renal function is a common consequence of myocardial infarction (MI) resulting in increased cardiovascular events, known as cardiorenal syndrome (CRS). Although molecular mechanisms contributing to CRS are not well understood, a role for elevated plasma levels of the uremic toxin indoxyl sulphate (IS) and increased fibrosis have been described. MicroRNAs are small endogenously transcribed regulatory RNAs that modulate gene expression and regulate many cardiac processes involved in cardiac dysfunction. Aim: Using a rat model we investigated whether MI leads to changes in expression of cardiac microRNA-21 and microRNA-29, both known to contribute to fibrosis. We also investigated the effect of lowering plasma uremic toxins on cardiac expression of these microRNAs. Methods: MI was induced by coronary artery ligation in male Sprague-Dawley rats. At 16 weeks cardiac function was measured prior to sacrifice. Cardiac tissues were assessed for molecular changes using real-time PCR, western blot analysis and histological methods. Results: MI significantly increased cardiac microRNA-21, collagen1A1, fibronectin-1 and TGFβ1 mRNA expression, as well as cardiac fibrosis and collagen 1 protein expression. Conversely, microRNA-29 expression was reduced in the heart (Table). Treatment with the AST-120 significantly reversed all these changes (Table). MicroRNA-21 levels significantly correlated with mRNA for TGF-β1 (P=0.049; r2=0.17) and its target genes collagen1A1 (P=0.004; r2=0.35) and fibronectin-1 (P=0.003; r2=0.52). MicroRNA-29b levels negatively and significantly correlated with TGF-β1 (P=0.017; r2=0.26) and collagen1A1 (P=0.048; r2=0.18) and fibronectin-1 (P=0.013; r2=0.29). Conclusions: We report a link between the beneficial effects of lowering circulating uremic toxins and microRNAs changes in the heart. Targeting microRNA’s may provide a therapeutic target for the treatment of CRS.

Abstract 331: Mir-433 Controls Cardiac Fibrosis

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Lichan Tao ◽  
Xiaoting Wu ◽  
Ping Chen ◽  
Shanshan Li ◽  
Xiaomin Zhang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Heart Diseases ◽  
Mice Model ◽  
Ki 67 ◽  
End Stage ◽  
Common Manifestation

Background: Cardiac fibrosis, a result of multiple injurious insults in heart, is a final common manifestation of chronic heart diseases and can lead to end-stage cardiac failure. MicroRNAs (miRNAs, miRs) participate in many essential biological processes and their dysfunction has been implicated in a variety of cardiovascular diseases including fibrosis. miR-433 has recently been implicated in renal fibrosis, however, its role in cardiac fibrosis is unclear. Methods and results: miR-433 was increased in heart samples from dilated cardiomyopathy patients as determined by qRT-PCRs. In addition, miR-433 was also consistently upregulated in mice model of cardiac fibrosis after myocardial infarction or heart failure. Additionally, miR-433 was found to be enriched in fibroblasts compared to cardiomyocytes. In neonatal cardiac fibroblasts, forced expression of miR-433 promoted cell proliferation as indicated by EdU and Ki-67 staining. Moreover, miR-433 overexpression promoted the transdifferentiation of fibroblasts into myofibroblasts as determined by qRT-PCR and western blot for α-SMA and collagen whether in the presence of TGF-β or not, indicating that miR-433 is sufficient to induce fibrosis. In addition, knockdown of miR-433 inhibited proliferation and the transdifferentiation into myofibroblasts, indicating that miR-433 is required for cardiac fibrosis. Interestingly, miR-433 did not affect the migration of cardiac fibroblast. Importantly, miR-433 antagomir could partially attenuate cardiac fibrosis induced by myocardial infarction in mice. Conclusion: both in vitro and in vivo. Inhibition of miR-433 represents a novel therapeutic strategy for cardiac fibrosis.

CGRP derived from cardiac fibroblasts is an endogenous suppressor of cardiac fibrosis

2019 ◽  
Vol 116 (7) ◽  
pp. 1335-1348 ◽  
Author(s):  
Wenqun Li ◽  
Zheng Zhang ◽  
Xiaohui Li ◽  
Jifeng Cai ◽  
Dai Li ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Cardiac Fibrosis ◽  
Nuclear Translocation ◽  
Cardiac Fibroblasts ◽  
Systolic Pressure ◽  
Allyl Isothiocyanate ◽  
Bioactive Substances ◽  
Beneficial Effects ◽  
Tgf Β1

Abstract Aims Aberrant activation of cardiac fibroblasts leads to cardiac fibrosis, and evolving evidences suggest that endogenous bioactive substances derived from cardiac fibroblasts regulate cardiac fibroblasts activation in an autocrine/paracrine manner. Here we first presented evidence that cardiac fibroblasts can synthesize and secrete calcitonin gene-related peptide (CGRP), therefore, this study aimed to investigate the role of cardiac fibroblasts-derived CGRP in cardiac fibroblasts activation and its regulative mechanism. Methods and results The abundantly expression of CGRP in rat, mouse, and human myocardium allowed us to explore the cellular origin of CGRP, and found that the cardiac CGRP was mainly derived from cardiac fibroblasts. Activating TRPA1 with a specific agonist allyl isothiocyanate promoted the synthesis and secretion of CGRP, as well as intracellular Ca2+. These effects were reversed by TRPA1-specific antagonist HC030031 and Ca2+ chelator BAPTA-AM. TGF-β1 was applied to induce the activation of cardiac fibroblasts, and found that TGF-β1 can increase the mRNA expression and secretion levels of CGRP in cardiac fibroblasts. Either CGRP8–37 (CGRP receptor antagonist) or α-CGRP small interfering RNA (siRNA) aggravated TGF-β1-induced proliferation, differentiation, collagen production, and instigated inflammation in cardiac fibroblasts. Moreover, TGF-β1-induced NF-κB activation including IκBα phosphorylation and p65 nuclear translocation were also promoted by CGRP8–37 and α-CGRP siRNA. NF-κB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) reversed the effects of CGRP8–37 on NF-κB activation. The promotive effects of CGRP8–37 on TGF-β1-induced activation of cardiac fibroblasts were all reversed by PDTC. Monocrotaline (MCT) induces pulmonary arterial hypertension, progressively leading to right ventricular fibrosis. This model of cardiac fibrosis was developed here to test the potentially beneficial effects of TRPA1 activation in vivo. The non-toxic TRPA1 agonist Cinnamaldehyde (CA) inhibited MCT-induced elevation in right ventricle systolic pressure, RV/LV + S, and right ventricular collagen accumulation, as well as down-regulation of CGRP. CA increased the synthesis and secretion of CGRP, and inhibited TGF-β1-induced activation in cardiac fibroblasts. Conclusion Our data suggested an autocrine role for cardiac fibroblasts-derived CGRP in suppressing activation of cardiac fibroblasts through inhibiting NF-κB activation. Increasing autocrine CGRP by activating TRPA1 can ameliorate cardiac fibrosis. These findings support the notion that CGRP derived from cardiac fibroblasts is an endogenous suppressor of cardiac fibrosis.

scholarly journals The association between RGS4 and choline in cardiac fibrosis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jing Guo ◽  
Pengzhou Hang ◽  
Jie Yu ◽  
Wen Li ◽  
Xiuye Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Western Blot ◽  
G Protein ◽  
Protein Level ◽  
Cardiac Fibrosis ◽  
Collagen I ◽  
Qrt Pcr ◽  
Tgf Β1

Abstract Background Myocardial fibrosis is caused by the adverse and powerful remodeling of the heart secondary to the death of cardiomyocytes after myocardial infarction. Regulators of G protein Signaling (RGS) 4 is involved in cardiac diseases through regulating G protein-coupled receptors (GPCRs). Methods Cardiac fibrosis models were established through cardiac fibroblasts (CFs) treatment with transforming growth factor (TGF)-β1 in vitro and mice subjected to myocardial infarction in vivo. The mRNA expression of RGS4, collagen I/III and α-SMA detected by qRT-PCR. Protein level of RGS4, collagen I, CTGF and α-SMA detected by Western blot. The ejection fraction (EF%) and fractional shortening (FS%) of mice were measured by echocardiography. Collagen deposition of mice was tested by Masson staining. Results The expression of RGS4 increased in CFs treatment with TGF-β1 and in MI mice. The model of cardiac fibrosis detected by qRT-PCR and Western blot. It was demonstrated that inhibition of RGS4 expression improved cardiac fibrosis by transfection with small interfering RNA in CFs and injection with lentivirus shRNA in mice. The protective effect of choline against cardiac fibrosis was counteracted by overexpression of RGS4 in vitro and in vivo. Moreover, choline inhibited the protein level of TGF-β1, p-Smad2/3, p-p38 and p-ERK1/2 in CFs treated with TGF-β1, which were restored by RGS4 overexpression. Conclusion This study demonstrated that RGS4 promoted cardiac fibrosis and attenuated the anti-cardiac fibrosis of choline. RGS4 may weaken anti-cardiac fibrosis of choline through TGF-β1/Smad and MAPK signaling pathways.

Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Deep Tissue ◽  
Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

Sign in / Sign up

Export Citation Format

Share Document