Caveolin 1 inhibits transforming growth factor-β1 activity via inhibition of Smad signaling by hypertrophic scar derived fibroblasts in vitro

Zhang, Guoyou; He, Bin; Liao, Tian; Luan, Qi; Tao, Cheng; Nie, Chunlei; Albers, Andreas E.; Zheng, Xin; Xie, Xue-guan; Gao, Weiyang

doi:10.1016/j.jdermsci.2010.10.018

Cited by 15 publications

(11 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, Gal-1 and smad2/3 siRNA inhibited COL-3 and COL-5 expression, and Gal-1-induced stimulation of FN and LM-5 expression was blocked by NF- κ B inhibitors. These results are supported by previous studies that activated Cav inhibits smad2/3 phosphorylation that is reduced by COL expression 45, 48 and that NF- κ B activation has relevance to regulate ECM proteins such as FN and LM as well as motility. 18, 45, 46 Therefore, our results strongly suggest that Cav-1-dependent smad2/3 dephosphorylation and PKC-dependent NF- κ B phosphorylation play an important role in Gal-1-reduced COL-3/-5 expression and Gal-1-induced FN/LM-5 expression in human UCB-MSCs.…”

Section: Discussionsupporting

confidence: 88%

Galectin-1 stimulates motility of human umbilical cord blood-derived mesenchymal stem cells by downregulation of smad2/3-dependent collagen 3/5 and upregulation of NF-κB-dependent fibronectin/laminin 5 expression

et al. 2014

Cell Death Dis

View full text Add to dashboard Cite

Galectin-1 (Gal-1) belongs to a family of endogenous lectins with conserved carbohydrate recognition domains binding β-galactosidase sugars and plays a vital role in regulating stem cell functions including determination of cell fate. However, our understanding of the functional roles of Gal-1 in human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) is still fragmentary and incomplete. Gal-1 significantly increased motility after a 24-h incubation, and this effect was inhibited by β-lactose. We analyzed 17 extracellular matrix (ECM) genes in UCB-MSCs. Gal-1 decreased the expression of collagen genes COL3A1 (COL-3) and COL5A1 (COL-5) but increased the expression of fibronectin (FN) and laminin 5 (LM-5), that were reversed by β-lactose. Gal-1 increased protein kinase C (PKC), c-Src, and caveolin-1 (Cav-1) phosphorylation that was attenuated by β-lactose and the Src inhibitor PP2. In addition, pretreatment with the lipid raft disruptor Mβ-CD and the PKC inhibitors inhibited Gal-1-induced UCB-MSC motility. In addition, Gal-1 reduced smad2/3 phosphorylation and induced nuclear factor (NF)-κB phosphorylation. Pretreatment with Mβ-CD attenuated Gal-1-reduced smad2/3 phosphorylation, COL-3, and COL-5 expression but did not affect NF-κB phosphorylation, FN, or LM-5 expression. In contrast, PKC inhibitors only attenuated NF-κB phosphorylation, FN, and LM-5 expression. Reconstructing Gal-1-induced genetic changes by replacing it with siRNA specific for COL-3 or COL-5, or treatment of the cells with FN and LM-5 proteins, increased motility and its related proteins such as focal adhesion kinase, Akt, Erk, integrins, and matrix metalloproteinase-2. A combined treatment with COL-3/COL-5 siRNA or FN/LM-5 compared with that of single treatments was synergistic. However, a single Gal-1 treatment maximally stimulated motility and related protein phosphorylation/expression. These results demonstrate that Gal-1 stimulated human UCB-MSC motility by decreasing COL-3/COL-5 expression and increasing FN/LM-5 expression through a PKC-dependent NF-κB and c-Src/Cav-1-dependent smad2/3 pathway that was critical for governing the activation of FAK, Akt, Erk, integrins, and MMP2.

show abstract

Section: Discussionsupporting

confidence: 88%

Galectin-1 stimulates motility of human umbilical cord blood-derived mesenchymal stem cells by downregulation of smad2/3-dependent collagen 3/5 and upregulation of NF-κB-dependent fibronectin/laminin 5 expression

et al. 2014

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Cav-1 is involved in control of the cell motility through interactions with the cell cytoskeleton on the inside and with extracellular matrix (ECM) on the outside. 17 Cav-1 demonstrates a negative correlation with the expression of collagen I, which is especially pronounced in scleroderma, 18 keloids, 19 hypertrophic scars, 20 and chronologically aged skin. 21 Also, Cav-1 scaffolding domain peptide was shown to demonstrate antifibrotic properties both in vitro and in vivo.…”

Section: Involvement Of Cav-1 In Epithelial Hyperproliferation and Inmentioning

confidence: 96%

Caveolin-1 as a pathophysiological factor and target in psoriasis

Kruglikov¹,

Scherer

2019

npj Aging Mech Dis

View full text Add to dashboard Cite

Low expression of caveolin-1 (Cav-1) is typical in psoriatic lesions and overexpression of Cav-1 leads to a reduction of inflammation and suppression of epidermal hyperproliferation, thus ameliorating these two well-known hallmarks of psoriasis. At the same time, the interfacial layers of the white adipose tissue (WAT) adjacent to psoriatic lesions demonstrate much higher stiffness, which also points to a modification of Cav-1 expression in this tissue. These processes are connected with each other and regulated via exosomal exchange. Here we discuss the role of Cav-1 expression in inflammatory and hyperproliferative processes and analyze the ways to provide spatially different modulation of Cav-1 expression in the skin and WAT. Such modulation can be induced by different pharmacological and physical factors. These include application of mechanical stress and supra-physiological temperatures. Cav-1 should therefore be considered as an important target in treatment of psoriasis.

show abstract

“…Moreover, caveolin is associated with cellular proliferation and cellular senescence . Caveolin is down‐regulated in rapidly dividing fibroblasts, while up‐regulation of caveolin expression may be involved in myofibroblast persistence via cellular senescence . Therefore, caveolin is involved in inhibition of the TGF‐β response via multiple regulatory mechanisms: receptor degradation, receptor expression, Smad phosphorylation, cellular proliferation, and cellular senescence.…”

Section: Introductionmentioning

confidence: 99%

Altered TGF‐β signaling in fetal fibroblasts: What is known about the underlying mechanisms?

Walraven

Gouverneur

Middelkoop

et al. 2013

Wound Repair Regeneration

View full text Add to dashboard Cite

Scarless wound healing is a unique and intrinsic capacity of the fetal skin that is not fully understood. Further insight into the underlying mechanisms of fetal wound healing may lead to new therapeutic approaches promoting adult scarless wound healing. Differences between fetal and adult wound healing are found in the extracellular matrix, the inflammatory reaction and the levels of growth factors present in the wound. This review focuses specifically on transforming growth factor β (TGF-β), as this growth factor is prominently involved in wound healing and fibroblast-to-myofibroblast differentiation. Although fetal fibroblasts do respond to TGF-β, they lack a proliferative and a contractile response and display short-lived myofibroblast differentiation, autocrine response, and collagen up-regulation in comparison with adult fibroblasts. Curiously, prolonged TGF-β activation is associated with fibrosis, and therefore, this short-lived response in fetal fibroblasts might contribute to scarless healing. This review gives an overview of the current knowledge on TGF-β signaling and the intracellular TGF-β signaling pathway in fetal fibroblasts. Furthermore, this review also describes the various components that regulate the cellular TGF-β response and hypothesizes about the possible roles these components might play in the altered response of fetal fibroblasts to TGF-β.

show abstract

Caveolin 1 inhibits transforming growth factor-β1 activity via inhibition of Smad signaling by hypertrophic scar derived fibroblasts in vitro

Cited by 15 publications

References 9 publications

Galectin-1 stimulates motility of human umbilical cord blood-derived mesenchymal stem cells by downregulation of smad2/3-dependent collagen 3/5 and upregulation of NF-κB-dependent fibronectin/laminin 5 expression

Galectin-1 stimulates motility of human umbilical cord blood-derived mesenchymal stem cells by downregulation of smad2/3-dependent collagen 3/5 and upregulation of NF-κB-dependent fibronectin/laminin 5 expression

Caveolin-1 as a pathophysiological factor and target in psoriasis

Altered TGF‐β signaling in fetal fibroblasts: What is known about the underlying mechanisms?

Contact Info

Product

Resources

About