Syndecan-1 regulates extracellular matrix expression in keloid fibroblasts via TGF-β1/Smad and MAPK signaling pathways

Cui, Jing; Jin, Songqing; Jin, Can; Jin, Zhehu

doi:10.1016/j.lfs.2020.117326

Cited by 24 publications

(21 citation statements)

References 26 publications

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“…The increased aortic tissue expression of Sdc-1 in T2D facilitates a potential role for an increased aortic Sdc-1 expression in the reduced prevalence of a thoracic AA in T2D [ 24 ]. Of potential interest here is that the knockdown of Sdc-1 inhibits pathways that upregulate the expression of importin-8 [ 37 , 38 ] and loss of function of importin-8 has been shown to cause a syndromic form of thoracic AA [ 39 ]. In addition, endothelial nuclear factor-κB (NF-κB) levels associate with a thoracic AA where NF-κB activation may trigger macrophage infiltration and inflammation in the adventitia and media [ 40 ] and Sdc-1 and GLP-1 alike have been shown to suppress NF-κB activation [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Syndecan-1 Expression Is Increased in the Aortic Wall of Patients with Type 2 Diabetes but Is Unrelated to Elevated Fasting Plasma Glucagon-Like Peptide-1

et al. 2021

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A reduced prevalence of a thoracic aortic aneurysm (thoracic AA) is observed in type 2 diabetes (T2D). Glucagon-like peptide-1 (GLP-1)/GLP-1-based anti-diabetic therapy has indicated protective effects in thoracic AA and regulates the processes controlling the vascular tissue expression of Syndecan-1 (Sdc-1). Sdc-1 expression on macrophages infiltrating the aortic tissue contributes to a counter-regulatory response to thoracic AA formation in animal models through the interplay with inflammation/proteolytic activity. We hypothesized that elevated fasting plasma GLP-1 (fpGLP-1) increases the aortic Sdc-1 expression in T2D, which may contribute to a reduced prevalence of thoracic AA. Consequently, we determined whether T2D/thoracic AA associates with an altered Sdc-1 expression in the aortic tissue and the possible associations with fpGLP-1 and inflammation/proteolytic activity. From a cohort of surgical patients with an aortic valve pathology, we compared different disease groups (T2D/thoracic AA) with the same sub-cohort group of controls (patients without T2D and thoracic AA). The MMP-2 activity and Sdc-1, GLP-1R and CD68 expression were analyzed in the aortic tissue. GLP-1, Sdc-1 and cytokines were analyzed in the plasma. The aortic Sdc-1 expression was increased in T2D patients but did not correlate with fpGLP-1. Thoracic AA was associated with an increased aortic expression of Sdc-1 and the macrophage marker CD68. CD68 was not detected in T2D. In conclusion, an increased aortic Sdc-1 expression may contribute to a reduced prevalence of thoracic AA in T2D.

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Section: Discussionmentioning

confidence: 99%

Syndecan-1 Expression Is Increased in the Aortic Wall of Patients with Type 2 Diabetes but Is Unrelated to Elevated Fasting Plasma Glucagon-Like Peptide-1

et al. 2021

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“…Additionally, the contribution of p38 and JNK pathways for TGF-β to activate renal brosis has been addressed [24,25]. Together with our current ndings, the p38 and JNK inhibitors may provide a potential target in the treatment of GO [21][22][23][24][25].…”

Section: Discussionmentioning

confidence: 75%

“…The TGF-β1-dependent MAPK pathway has been implicated in stimulating myo broblasts transdifferentiation from broblasts and subsequent ECM production in several brotic pathologies. Cui et al [21] illustrated that p38 and ERK mediated TGF-β1-induced overexpression of the ECM in keloid broblasts. Yu et al [22] proposed that TGF-β1 activated hepatic stellate cells via p38 and ERK pathways in liver brosis.…”

Section: Discussionmentioning

confidence: 99%

JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblasts Transdifferentiation in Graves' Orbital Fibroblasts

Hou

Kau

et al. 2021

Preprint

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Transforming growth factor-β1 (TGF-β1)-induced myofibroblasts transdifferentiation from orbital fibroblasts is known to dominate tissue remodeling and fibrosis in Graves’ ophthalmopathy (GO). However, the signaling pathway through which TGF-β1 activates Graves’ orbital fibroblasts is unclear. This study investigated the role of mitogen-activated protein kinase (MAPK) pathways in TGF-β1-induced myofibroblasts transdifferentiation of Graves’ orbital fibroblasts. MAPK pathways were assessed by measuring the phosphorylation levels of p38, c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK) using Western blot analysis. The expression levels of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), fibronectin, and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-3) representing fibrogenesis processes were analysed. Specific pharmacologic kinase inhibitors were used to confirm the involvement of MAPK pathways. After treating Graves’ orbital fibroblasts with TGF-β1, the phosphorylation levels of p38 and JNK but not ERK were increased. Meanwhile, CTGF, α-SMA and fibronectin were overexpressed. After pre-incubation with p38, JNK and ERK inhibitors respectively, the TGF-β1-induced expression of CTGF, α-SMA, fibronectin, TIMP-1 and TIMP3 was abolished by p38 and JNK inhibitors but not ERK inhibitors. This study confirmed TGF-β1-induced myofibroblasts transdifferentiation in Graves' orbital fibroblasts via p38 and JNK signaling. Thus, MAPK pathways may be potential targets for the management of GO.

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“…In the research setting, biomarkers have been developed for this matter, remarkably syndecan‐1 (CD138), a cell surface proteoglycan that is expressed in differentiating keratinocytes and transiently upregulated in all layers of the epidermis upon tissue injury 28,29 . Syndecan‐1 regulates the expression of the ECM in keloid fibroblasts via TGF‐β1/Smad and mitogen‐activated protein kinase signaling pathways and have been found significantly overexpressed in keloids compared to hypertrophic scars or normal skin and completely absent in dermatofibrosarcoma protuberans 28,30 . It has been shown that the knockdown of syndecan‐1 reduces the proliferation of keloid fibroblasts and the content of the ECM 30 …”

Section: Introductionmentioning

confidence: 99%

“…Syndecan‐1 regulates the expression of the ECM in keloid fibroblasts via TGF‐β1/Smad and mitogen‐activated protein kinase signaling pathways and have been found significantly overexpressed in keloids compared to hypertrophic scars or normal skin and completely absent in dermatofibrosarcoma protuberans 28,30 . It has been shown that the knockdown of syndecan‐1 reduces the proliferation of keloid fibroblasts and the content of the ECM 30 …”

Section: Introductionmentioning

confidence: 99%

Hypertrophic scars and keloids—Treatment with fractional lasers

Aristizabal¹,

Ayala-Bernal

2020

Dermatological Reviews

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Hypertrophic scars and keloids are frequent causes of dermatological consultation that impair function and cosmesis. Besides traditional therapies, lasers, and particularly fractional lasers (FLs), have emerged as readily available instruments to treat a variety of dermatological and aesthetic ailments including scars. In this review, the use of FLs in the treatment of hypertrophic and keloid scars is summarized in detail. Practitioners should be aware of the use of lasers as key devices in the treatment protocols of hypertrophic and keloid scars.

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Syndecan-1 regulates extracellular matrix expression in keloid fibroblasts via TGF-β1/Smad and MAPK signaling pathways

Cited by 24 publications

References 26 publications

Syndecan-1 Expression Is Increased in the Aortic Wall of Patients with Type 2 Diabetes but Is Unrelated to Elevated Fasting Plasma Glucagon-Like Peptide-1

Syndecan-1 Expression Is Increased in the Aortic Wall of Patients with Type 2 Diabetes but Is Unrelated to Elevated Fasting Plasma Glucagon-Like Peptide-1

JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblasts Transdifferentiation in Graves' Orbital Fibroblasts

Hypertrophic scars and keloids—Treatment with fractional lasers

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