Angiotensin II stimulates canonical TGF-β signaling pathway through angiotensin type 1 receptor to induce granulation tissue contraction

Ehanire, Tosan; Ren, Lixia; Bond, Jennifer; Medina, Manuel A.; Li, George; Bashirov, Latif; Chen, Lei; Kokosis, George; Ibrahim, Mohamed M.; Selim, Angelica; Blobe, Gerard C.; Levinson, Howard

doi:10.1007/s00109-014-1211-9

Cited by 47 publications

(39 citation statements)

References 31 publications

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“…It has been largely demonstrated that TGF-beta serves as a key downstream mediator in Ang II-induced chronic renal fibrosis (Iekushi et al, 2011). Fibrosis resulting in the excessive synthesis and accumulation of interstitial matrix proteins could be induced by Ang II via the upregulation of TGF-beta (Ehanire et al, 2015a;Ding et al, 2019). Consistent with these findings, our data showed that following Ang II infusion, the expression of fibrotic markers alpha-SMA, MMP-2, and MMP-9 were all significantly increased (Figures 1A-F).…”

Section: Discussionmentioning

confidence: 99%

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Zhang

Fan

Cai

et al. 2020

Front. Cell Dev. Biol.

168

130

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Fibrosis is a common phenotype that often leads to the progression of blood pressure-induced chronic kidney disease (CKD). TGF-beta plays an important role in promoting pathogenesis, and NLRP3 is a critical mediator in the progression of blood pressure-induced CKD. However, the pathophysiological roles of the TGF-betamediated NLRP3 pathway in modulating fibrosis in blood pressure-induced CKD have not been elucidated. The present study aims to investigate the contribution of TGFbeta-mediated NLRP3 inflammasome to renal fibrosis in rats with high blood pressure. By treating rats with angiotensin II (Ang II) for 14 days, we observed the development of fibrosis, characterized by epithelial-mesenchymal transition (EMT) markers [alphasmooth muscle actin (alpha-SMA), MMP-2, and MMP-9]. Immunohistochemical analysis further revealed that TGF-beta and NLRP3 inflammasome activation [high-mobility group box 1 (HMGB1), IL-1beta, and NLRP3] were significantly upregulated in the kidney of rats with Ang II-induced hypertension. Interestingly, we observed that Ang II could not increase the production of NLRP3 proteins, but TGF-beta could induce NLRP3 protein expression in cultured NRK-52E cells. Furthermore, we speculated that TGF-beta played a pathogenic role in Ang II-induced CKD because TGF-beta induced the activation of NLRP3 inflammasomes and Gasdermin D cleavage expression. We also proved that the pharmacological inhibition of NLRP3 by ISO caused a decrease in TGF-beta-induced NLRP3 inflammasome activation and the expression of EMT markers (alpha-SMA and CollagenI) and Gasdermin D cleavage. Collectively, these results suggest that TGF-beta-mediated NLRP3 inflammasome activation may cause the release of HMGB1 and an increase in Gasdermin D cleavage in NRK-52E, thereby contributing to renal fibrosis in Ang II-induced CKD. These findings provide novel insights into the pathogenic role of NLRP3 in CKD associated with high blood pressure.

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Section: Discussionmentioning

confidence: 99%

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Zhang

Fan

Cai

et al. 2020

Front. Cell Dev. Biol.

168

130

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“…The male diabetic (BSK.Cg-m+/+Lepr db ; db/db) and WT mice (C57BL/6J) were 10 weeks old at the beginning of the experiments; db/db mice weighed 55-60 g with average blood glucose levels of 26.8 ± 0.6 mmol/L and WT mice weighed 20-25 g with average blood glucose levels of 6.1 ± 0.4 mmol/L. The skin wound study was performed as previously described [29]. Briefly, after shaving the chosen area of the dorsal surface under anesthesia, a circular fullthickness excisional skin wound of 8-mm diameter was created using a surgical punch.…”

Section: Wound Healing In Vivomentioning

confidence: 99%

Cinnamaldehyde accelerates wound healing by promoting angiogenesis via up-regulation of PI3K and MAPK signaling pathways

Xing¹,

Lin²,

Fu³

et al. 2018

Laboratory Investigation

108

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The bark of Cinnamomum cassia (C. cassia) has been used for the management of coronary heart disease (CHD) and diabetes mellitus. C. cassia may target the vasculature, as it stimulates angiogenesis, promotes blood circulation and wound healing. However, the active components and working mechanisms of C. cassia are not fully elucidated. The Shexiang Baoxin pill (SBP), which consists of seven medicinal materials, including C. cassia etc., is widely used as a traditional Chinese patent medicine for the treatment of CHD. Here, 22 single effective components of SBP were evaluated against the human umbilical vein endothelial cells (HUVECs). We demonstrated that in HUVECs, cinnamaldehyde (CA) stimulated proliferation, migration, and tube formation. CA also activated the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Furthermore, the secretion of vascular endothelial growth factor (VEGF) from HUVECs was increased by CA. In vivo, CA partially restored intersegmental vessels in zebrafish pretreated with PTK787, which is a selective inhibitor for vascular endothelial growth factor receptor (VEGFR). CA also showed pro-angiogenic efficacy in the Matrigel plug assay. Additionally, CA attenuated wound sizes in a cutaneous wound model, and elevated VEGF protein and CD31-positive vascular density at the margin of these wounds. These results illustrate that CA accelerates wound healing by inducing angiogenesis in the wound area. The potential mechanism involves activation of the PI3K/AKT and MAPK signaling pathways. Such a small non-peptide molecule may have clinical applications for promoting therapeutic angiogenesis in chronic diabetic wounds and myocardial infarction.

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“…This can also be explained by up-regulation of TGF-β, because TGF-β has been reported to stimulate differentiation of fibroblasts to myofibroblasts [ 23 ], which play a major role in tissue shrinking/contraction in the wound healing process. Also, it was reported that stimulation of the TGF-β signaling pathway by angiotensin II induces granulation tissue contraction via the angiotensin type 1 receptor [ 51 ]. Thus, the present data also showed that induction of TGF-β by topical application of lavender oil promotes not only formation of granulation tissue, but also wound shrinking/contraction.…”

Section: Discussionmentioning

confidence: 99%

Wound healing potential of lavender oil by acceleration of granulation and wound contraction through induction of TGF-β in a rat model

Mori

Kawanami

Kawahata

et al. 2016

BMC Complement Altern Med

113

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BackgroundAlthough previous studies have suggested that lavender oil promote wound healing, no study has examined the molecular mechanisms of its effect. In this study, we investigated the effect of lavender oil on various steps of wound healing and its molecular mechanism, focusing on transforming growth factor-β (TGF-β).MethodsCircular full-thickness skin wounds were produced on rats. Control solution or lavender oil was topically applied to the wounds on alternating days for 14 days.ResultsThe area of wounds topically treated with lavender oil was significantly decreased as compared to that of wounds of control rats at 4, 6, 8, and 10 days after wounding. Topical application of lavender oil induced expression of type I and III collagen at 4 days after wounding, accompanied by an increased number of fibroblasts, which synthesize collagen. Induced expression of type III collagen by topical application of lavender oil was reduced to control level at 7 days after wounding although increased expression of type I collagen still continued even at 7 days, suggesting rapid collagen replacement from type III to type I in wounds treated with lavender oil. Importantly, expression of TGF-β in wounds treated with lavender oil was significantly increased as compared to control. Moreover, an increased number of myofibroblasts was observed in wounds treated with lavender oil at 4 days after wounding, suggesting promotion of differentiation of fibroblasts through induction of TGF-β, which is needed for wound contraction.ConclusionThis study demonstrated that topical application of lavender oil promoted collagen synthesis and differentiation of fibroblasts, accompanied by up-regulation of TGF-β. These data suggest that lavender oil has the potential to promote wound healing in the early phase by acceleration of formation of granulation tissue, tissue remodeling by collagen replacement and wound contraction through up-regulation of TGF-β. The beneficial effect of lavender oil on wound healing may raise the possibility of new approaches as complementary treatment besides conventional therapy.

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Angiotensin II stimulates canonical TGF-β signaling pathway through angiotensin type 1 receptor to induce granulation tissue contraction

Cited by 47 publications

References 31 publications

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

Cinnamaldehyde accelerates wound healing by promoting angiogenesis via up-regulation of PI3K and MAPK signaling pathways

Wound healing potential of lavender oil by acceleration of granulation and wound contraction through induction of TGF-β in a rat model

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