The differential proliferative response of fetal and adult human skin fibroblasts to TGF-β is retained when cultured in the presence of fibronectin or collagen

Armatas, Andreas A.; Pratsinis, Harris; Mavrogonatou, Eleni; Angelopoulou, Maria T.; Kouroumalis, Anastasios; Karamanos, Nikos K.; Kletsas, Dimitris

doi:10.1016/j.bbagen.2014.04.004

Cited by 14 publications

(9 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…siRNA-mediated knocking down of human p53 and Smad4 was performed as described previously [ 82 , 83 ]. Human breast stromal fibroblasts were plated and grown in DMEM containing 10% (v/v) FBS for 24 h before siRNA transfection.…”

Section: Methodsmentioning

confidence: 99%

Ionizing radiation-mediated premature senescence and paracrine interactions with cancer cells enhance the expression of syndecan 1 in human breast stromal fibroblasts: the role of TGF-β

Liakou

Mavrogonatou

Pratsinis

et al. 2016

Aging

Self Cite

View full text Add to dashboard Cite

The cell surface proteoglycan syndecan 1 (SDC1) is overexpressed in the malignant breast stromal fibroblasts, creating a favorable milieu for tumor cell growth. In the present study, we found that ionizing radiation, a well-established treatment in human breast cancer, provokes premature senescence of human breast stromal fibroblasts in vitro, as well as in the breast tissue in vivo. These senescent cells were found to overexpress SDC1 both in vitro and in vivo. By using a series of specific inhibitors and siRNA approaches, we showed that this SDC1 overexpression in senescent cells is the result of an autocrine action of Transforming Growth Factor-β (TGF-β) through the Smad pathway and the transcription factor Sp1, while the classical senescence pathways of p53 or p38 MAPK - NF-kB are not involved. In addition, the highly invasive human breast cancer cells MDA-MB-231 (in contrast to the low-invasive MCF-7) can also enhance SDC1 expression, both in early-passage and senescent fibroblasts via a paracrine action of TGF-β. The above suggest that radiation-mediated premature senescence and invasive tumor cells, alone or in combination, enhance SDC1 expression in breast stromal fibroblasts, a poor prognostic factor for cancer growth, and that TGF-β plays a crucial role in this process.

show abstract

Section: Methodsmentioning

confidence: 99%

Ionizing radiation-mediated premature senescence and paracrine interactions with cancer cells enhance the expression of syndecan 1 in human breast stromal fibroblasts: the role of TGF-β

Liakou

Mavrogonatou

Pratsinis

et al. 2016

Aging

Self Cite

View full text Add to dashboard Cite

show abstract

“…This mechanism should also exist in other organisms on the basis that both HuR and the ARE in the TGF-β1 3′UTR are conserved among various species. Increased TGF-β1 would induce a cascade of the fibrogenic response in both the canonical Smad-dependent signaling pathway and non-Smad pathways by inducing the expression of collagen, fibronectin and other ECM molecules [ 4 ]. However, we have only tested a limited indicator of remodeling, Col-I and α-SMA.…”

Section: Discussionmentioning

confidence: 99%

“…TGF-β1, a pleiotropic cytokine that had been evidenced to be involved in the synthesis of matrix molecules in the ASM cells, especially on the synthesis of collagen types I, III, IV, VII and X, fibronectin and proteoglycans [ 4 ], has been implicated in the pathogenesis of airway remodeling in asthma [ 5 – 7 ]. For years, the mechanisms underlying the development of fibrosis have been extensively studied and multiple signal pathways are involved in, such as the integrin α5β6 [ 8 ], phosphatidylcholine-specific phospholipase C, protein kinase C-delta [ 9 ], the integrin receptor α5β1 [ 10 ], the canonical Smad-dependent signaling pathway [ 11 ] and p38 MAPK [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

A HuR/TGF-β1 feedback circuit regulates airway remodeling in airway smooth muscle cells

et al. 2016

View full text Add to dashboard Cite

BackgroundAsthma is a worldwide health burden with an alarming prevalence. For years, asthma-associated airway injury remains elusive. Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that has been shown to be involved in the synthesis of the matrix molecules associated with airway remodeling. Human antigen R (HuR), the member of the Hu RNA-binding protein family, can bind to a subset of short-lived mRNAs in their 3′ untranslated regions (UTR). However, the functional roles and relevant signaling pathways of HuR in airway remodeling have not been well illustrated. Thus, we aim to explore the relationship between HuR and TGF-β1 in platelet derived growth factor(PDGF)-induced airway smooth muscle (ASM) cells and asthmatic animal.MethodsCultured human ASM cells were stimulated by PDGF for 0, 6, 12 and 24 h. Western blotting, RT-PCR and immunofluoresence were used to detect the expression of HuR, TGF-β1, α-smooth muscle actins (α-SMA) and collagen type I (Col-I). Then knockdown of HuR, flow cytomerty was used to detect the morphological change and western blotting for functionally change of ASM cells. Furthermore, the interference of TGF-β1 and exogenous TGF-β1 were implemented to testify the influence on HuR. A murine OVA-driven allergic model based on sensitization and challenge was developed. The inflammatory response was measured by bronchoalveolar lavage fluid (BALF), airway damage was analyzed by hematoxylin and eosin staining, airway remodeling was assessed by sirius red staining and periodic acid-schiff staining, the expression level of HuR, TGF-β1 and α-SMA were measured by RT-PCR, western blotting and immunohistochemistry.ResultsHere, we found that PDGF elevated HuR expression both at mRNA and protein level in cultured ASM cells at a time-dependent manner, which was simultaneously accompanied by the enhanced expression of TGF-β1, α-SMA and Col-I. Further study revealed that the knockdown of HuR significantly increased the apoptosis of ASM cells and dampened TGF-β1, Col-I and α-SMA expression. However, interfering TGF-β1 with siRNA or extra addition of TGF-β1, HuR could restore its production as well as Col-I. Compared with normal mice stimulating with PBS, OVA-induced mice owned high amount of inflammatory cells, such as eosinophils, lymphocytes and neutrophils except macrophages. HE staining showed accumulation of inflammatory cells surrounding bronchiole and sirius red staining distinguished collagen type I and III deposition around the bronchiole. Higher abundance of HuR, TGF-β1 and α-SMA were verified in OVA-induced mice than PBS-induced mice by RT-PCR, western blotting and immunohistochemistry.ConclusionsA HuR/TGF-β1 feedback circuit was established to regulate airway remodeling in vivo and in vitro and targeting this feedback has considerable potential for the intervention of asthma.

show abstract

“…19 Relevant to the increased density of fibroblasts and COLIV deposition in the carrier biopsies, TGFβ has been linked to enhanced proliferation of adult skin fibroblasts. 20 Phosphorylation of SMAD2/3 is a well documented downstream event in the TGFβ signaling pathway. 18 We examined pSMAD2/3 immunoreactivity in the carrier and control biopsies to see whether we could detect evidence of elevated TGFβ signaling in the carrier biopsies.…”

Section: Psmad2/3 Immunoreactivity In Carrier Biopsiesmentioning

confidence: 99%

“…Phosphorylated SMAD2/3 then forms a complex with SMAD4 that shuttles to the nucleus and stimulates the transcription of several genes, eg, those of collagen. 20,47,48 We examined the distribution of pSMAD2/3 in the skin biopsies from the carriers and controls. The results showed that the denser population of fibroblasts in the carrier skin biopsies displayed nuclear immunoreactivity for pSMAD2/3.…”

Section: Similarities With Other Skin Disordersmentioning

confidence: 99%

Pathological changes in basement membranes and dermal connective tissue of skin from patients with hereditary cystatin C amyloid angiopathy

Snorradottir

Ísaksson

Ingþórsson

et al. 2017

Laboratory Investigation

View full text Add to dashboard Cite

Hereditary cystatin C amyloid angiopathy (HCCAA) is a genetic disease caused by a mutation in the cystatin C gene. Cystatin C is abundant in cerebrospinal fluid and the most prominent pathology in HCCAA is cerebral amyloid angiopathy due to mutant cystatin C amyloid deposition with associated cerebral hemorrhages, typically in young adult carriers. Analyses of post-mortem brain samples shows that pathological changes are limited to arteries and regions adjacent to arteries. The severity of pathological changes at post-mortem has precluded the elucidation of the evolution of histological changes. Mutant cystatin C deposition in carriers is systemic and has, for example, been described in the skin, suggesting similar pathological mechanisms both in the brain and outside of the central nervous system. The aim of this study was to use skin biopsies from asymptomatic and symptomatic carriers to study intermediate events in HCCAA pathogenesis. We found that cystatin C deposition in minimally affected samples was limited to the basement membrane (BM) between the dermis and epidermis. When the deposits were more advanced, they extended to other BM regions in the skin. Our results showed that the immunoreactivity of the BM protein COLIV was increased to a similar extent in all carrier biopsies and cystatin C deposits were in close association with COLIV. The density of fibroblasts in the upper dermis of carrier skin was increased, whereas the distribution of other cell types examined did not differ compared with control biopsies. COLIV and cystatin C immunoreactivity in carrier biopsies was closely associated with the fibroblasts. The results of this study, in conjunction with our previous results regarding pathological BM changes in leptomeningeal arteries of patients, suggest that BM changes are early and important events in HCCAA pathogenesis that could facilitate cystatin C deposition and aggregation.

show abstract

The differential proliferative response of fetal and adult human skin fibroblasts to TGF-β is retained when cultured in the presence of fibronectin or collagen

Cited by 14 publications

References 60 publications

Ionizing radiation-mediated premature senescence and paracrine interactions with cancer cells enhance the expression of syndecan 1 in human breast stromal fibroblasts: the role of TGF-β

Ionizing radiation-mediated premature senescence and paracrine interactions with cancer cells enhance the expression of syndecan 1 in human breast stromal fibroblasts: the role of TGF-β

A HuR/TGF-β1 feedback circuit regulates airway remodeling in airway smooth muscle cells

Pathological changes in basement membranes and dermal connective tissue of skin from patients with hereditary cystatin C amyloid angiopathy

Contact Info

Product

Resources

About