Epigallocatechin-3-gallate inhibits lysophosphatidic acid-stimulated connective tissue growth factor via JNK and Smad3 suppression in human gingival fibroblasts

Wang, Chen-Ying; Deng, Yi; Huang, Shih-Yung; Liu, Cheing-Meei; Chang, Hao-Hueng; Wong, Man-Ying

doi:10.1016/j.jfma.2012.04.004

Cited by 8 publications

(6 citation statements)

References 33 publications

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“…Thrombin treatment activated JNK, while curcumin inhibited CCN2 expression through JNK suppression. CCN2 is also induced by lysophosphatidic acid (LPA), in oral epithelial cells and gingival fibroblasts [128,129] and this effect can be significantly inhibited by TGFβ type I receptor/ALK5, Smad3, and JNK inhibitors but not ERK, P38, and MAPK inhibitors [129,130]. It has been proposed that LPA produced due to surgical wounds could contribute to the recurrence of gingival overgrowth by upregulating CCN2 expression in HGFs, an effect that is mediated by Smad3 and JNK activation and ALK5 transactivation [130], further highlighting the role of JNK in regulating cellular responses in gingival overgrowth.…”

Section: Gingival Fibroblasts and Jnkmentioning

confidence: 99%

JNK Signaling as a Key Modulator of Soft Connective Tissue Physiology, Pathology, and Healing

Nikoloudaki

Brooks

Peidl

et al. 2020

IJMS

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In healthy individuals, the healing of soft tissues such as skin after pathological insult or post injury follows a relatively predictable and defined series of cell and molecular processes to restore tissue architecture and function(s). Healing progresses through the phases of hemostasis, inflammation, proliferation, remodeling, and concomitant with re-epithelialization restores barrier function. Soft tissue healing is achieved through the spatiotemporal interplay of multiple different cell types including neutrophils, monocytes/macrophages, fibroblasts, endothelial cells/pericytes, and keratinocytes. Expressed in most cell types, c-Jun N-terminal kinases (JNK) are signaling molecules associated with the regulation of several cellular processes involved in soft tissue wound healing and in response to cellular stress. A member of the mitogen-activated protein kinase family (MAPK), JNKs have been implicated in the regulation of inflammatory cell phenotype, as well as fibroblast, stem/progenitor cell, and epithelial cell biology. In this review, we discuss our understanding of JNKs in the regulation of cell behaviors related to tissue injury, pathology, and wound healing of soft tissues. Using models as diverse as Drosophila, mice, rats, as well as human tissues, research is now defining important, but sometimes conflicting roles for JNKs in the regulation of multiple molecular processes in multiple different cell types central to wound healing processes. In this review, we focus specifically on the role of JNKs in the regulation of cell behavior in the healing of skin, cornea, tendon, gingiva, and dental pulp tissues. We conclude that while parallels can be drawn between some JNK activities and the control of cell behavior in healing, the roles of JNK can also be very specific modes of action depending on the tissue and the phase of healing.

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Section: Gingival Fibroblasts and Jnkmentioning

confidence: 99%

JNK Signaling as a Key Modulator of Soft Connective Tissue Physiology, Pathology, and Healing

Nikoloudaki

Brooks

Peidl

et al. 2020

IJMS

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“…Our previous data revealed that Rac1/ERK-dependent AP-1 activation participated in CXCL12-caused CTGF expression in WI-38 cells [ 17 ]. In addition, a previous study showed that activation of SMAD also participates in lysophosphatidic acid (LPA)-stimulated CTGF expression in gingival fibroblasts [ 45 ]. This paper exhibited that SMAD3 activation participated in CXCL12-stimulated CTGF expression in human lung fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, a previous research paper exhibited that TGF-β enhances CXCL12-induced chemotaxis and homing of naive T cells [ 47 ]. Several studies indicated that CTGF induction by LPA requires transactivation of ALK5 in mouse skeletal muscles and human gingival fibroblasts [ 45 , 48 ]. In contrast, a previous article indicated that angiotensin II mediates CTGF expression via SMAD phosphorylation, which is a TGF-β-independent mechanism [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

MEKK1, JNK, and SMAD3 mediate CXCL12-stimulated connective tissue growth factor expression in human lung fibroblasts

et al. 2018

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BackgroundIn idiopathic pulmonary fibrosis, the interaction of CXCL12 and CXC receptor 4 (CXCR4) plays a critical role in lung fibrosis. Connective tissue growth factor (CTGF) overexpression underlies the development of pulmonary fibrosis. Our previous report showed that the Rac1-dependent extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and activator protein (AP)-1 pathways are involved in CXCL12-generated CTGF expression in human lung fibroblasts (WI-38). In present study, we additionally inspected the involvement of mitogen-activated protein kinase kinase kinase 1 (MEKK1)/JNK-dependent SMAD3 in CXCL12-triggered CTGF expression in WI-38 cells.MethodsWI-38 cells were stimulated with CXCL12 in the absence or presence of specific inhibitors or small interfering RNAs (siRNAs). CTGF expression and signaling transduction molecules were assessed by Western blot, luciferase activity assay, or ChIP assay.ResultsCXCL-12-induced CTGF expression was attenuated by SIS3 (a SMAD3 inhibitor) and SMAD3 siRNA, but not by SB431542 (an activin receptor-like kinase 5, ALK5, inhibitor). CXCL12-stimulated CTGF expression was also attenuated by MEKK1 siRNA. Treatment of cells with CXCL12 caused an increase in SMAD3 phosphorylation at Ser208, translocation to nuclei, SMAD3-luciferase activity, and recruitment of SMAD3 to the CTGF promoter. Stimulation of cells with CXCL12 resulted in increase in JNK phosphorylation at Thr183/Tyr185 and MEKK1 phosphorylation at Thr261. Moreover, CXCL12-mediated SMAD3 phosphorylation or SMAD3-luciferase activity was inhibited by MEKK1 siRNA or SP600125. Finally, CXCL12-mediated JNK phosphorylation was attenuated by MEKK1 siRNA.ConclusionIn conclusion, results of this study suggest that CXCL12 activates the MEKK1/JNK signaling pathway, which in turn initiates SMAD3 phosphorylation, its translocation to nuclei, and recruitment of SMAD3 to the CTGF promoter, which ultimately induces CTGF expression in human lung fibroblasts.

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“…It has been shown that EGCG reduced the expression of CTGF and pro‐fibrotic molecules such as TGF‐β1 . Inhibition of TGF‐β1 by EGCG could result in a reduction of ECM synthesis and HSs formation .…”

Section: Traditional Plant‐based Medicine and Productsmentioning

confidence: 99%

“…48 It has been shown that EGCG reduced the expression of CTGF and pro-fibrotic molecules such as TGF-β1. 49 Inhibition of TGF-β1 by EGCG could result in a reduction of ECM synthesis and HSs formation. 50 And EGCG relieved cardiac fibrosis through low expression of CTGF, suggesting the therapeutic potential on the prevention of multiple fibrotic diseases including scaring.…”

Section: Traditional Plant-based Medicine and Productsmentioning

confidence: 99%

Biological approaches for hypertrophic scars

Zhong

2019

International Wound Journal

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Scar formation is usually the pathological consequence of skin trauma. And hypertrophic scars (HSs) frequently occur in people after being injured deeply. HSs are unusually considered as the result of tissue contraction and excessive extracellular matrix component deposition. Myofibroblasts, as the effector cells, mainly differentiated from fibroblasts, play the crucial role in the pathophysiology of HSs. A number of growth factors, inflammatory cytokines involved in the process of HS occurrence. Currently, with in‐depth exploration and clinical research of HSs, various creative and effective treatments budded. In here, we summarize the progress in the molecular mechanism of HSs, and review the available biotherapeutic methods for their pathophysiological characteristics. Additionally, we further prospected that the comprehensive therapy may be more suitable for HS treatment.

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Epigallocatechin-3-gallate inhibits lysophosphatidic acid-stimulated connective tissue growth factor via JNK and Smad3 suppression in human gingival fibroblasts

Cited by 8 publications

References 33 publications

JNK Signaling as a Key Modulator of Soft Connective Tissue Physiology, Pathology, and Healing

JNK Signaling as a Key Modulator of Soft Connective Tissue Physiology, Pathology, and Healing

MEKK1, JNK, and SMAD3 mediate CXCL12-stimulated connective tissue growth factor expression in human lung fibroblasts

Biological approaches for hypertrophic scars

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