Effects of IGFBP-1 and IGFBP-2 and their fragments on migration and IGF-induced proliferation of human dermal fibroblasts

Brandt, Katrin; Grünler, Jacob; Brismar, Kerstin; Wang, Jing

doi:10.1016/j.ghir.2014.11.001

Cited by 32 publications

(27 citation statements)

References 38 publications

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“…IGFBP2 is thought to be an important regulator of wound healing by its effect promoting proliferation and differentiation of fibroblasts and myoblasts. [ 20 , 21 ] In agreement with previous findings that FST (follistatin) is upregulated in muscle biopsy samples form COL6-RD individuals, in our study, FST in dermal fibroblasts is significantly upregulated (log 2 fold change +1.4 in DN and +1.2 in Null). FST is of particular interest since follistatin is a natural myostatin antagonist and has been proposed as a target for treatment of muscular dystrophy by promotion of muscle growth and decreasing fibrosis.…”

Section: Discussionsupporting

confidence: 93%

Transcriptome profiling identifies regulators of pathogenesis in collagen VI related muscular dystrophy

Butterfield

Dunn

et al. 2017

PLoS ONE

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ObjectivesThe collagen VI related muscular dystrophies (COL6-RD), Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) are among the most common congenital muscular dystrophies and are characterized by distal joint laxity and a combination of distal and proximal joint contractures. Inheritance can be dominant negative (DN) or recessive depending on the type and location of the mutation. DN mutations allow incorporation of abnormal chains into secreted tetramers and are the most commonly identified mutation type in COL6-RD. Null alleles (nonsense, frameshift, and large deletions) do not allow incorporation of abnormal chains and act recessively. To better define the pathways disrupted by mutations in collagen VI, we have used a transcriptional profiling approach with RNA-Seq to identify differentially expressed genes in COL6-RD individuals from controls.MethodsRNA-Seq allows precise detection of all expressed transcripts in a sample and provides a tool for quantification of expression data on a genomic scale. We have used RNA-Seq to identify differentially expressed genes in cultured dermal fibroblasts from 13 COL6-RD individuals (8 dominant negative and 5 null) and 6 controls. To better assess the transcriptional changes induced by abnormal collagen VI in the extracellular matrix (ECM); we compared transcriptional profiles from subjects with DN mutations and subjects with null mutations to transcriptional profiles from controls.ResultsDifferentially expressed transcripts between COL6-RD and control fibroblasts include upregulation of ECM components and downregulation of factors controlling matrix remodeling and repair. DN and null samples are differentiated by downregulation of genes involved with DNA replication and repair in null samples.ConclusionsDifferentially expressed genes identified here may help identify new targets for development of therapies and biomarkers to assess the efficacy of treatments.

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Section: Discussionsupporting

confidence: 93%

Transcriptome profiling identifies regulators of pathogenesis in collagen VI related muscular dystrophy

Butterfield

Dunn

et al. 2017

PLoS ONE

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“…Similarly, other studies focusing on human dermal broblasts identi ed that IGFBP-2 inhibited IGF-induced broblastic proliferation [25,32,33]. Of note, the inhibitory effect of IGFBP-2 was reduced when it was cleaved by metalloproteases like MMP-9 [34], which was also increased in our present study in SSc group. Accordingly, increased MMP-9 levels due to neutrophilic activation could reduce simultaneously the regulatory effect of IGFBP-2.…”

Section: Discussionsupporting

confidence: 84%

“…The main IGFBPs described in ILD context are IGFBP-1 and IGFBP-2. It has been shown that IGFBP-1 and − 2 were able to improve tissue repair in in ammatory conditions by increasing broblast proliferation and migration [27]. In SSc context, IGF-1 and IGFBP-3 are involved in abnormal repair process [28,29].…”

Section: Introductionmentioning

confidence: 99%

Serum IGFBP-2 in Systemic Sclerosis as a Protective Factor of Lung Dysfunction

Guiot

Njock

Andre

et al. 2020

Preprint

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Background Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the progression of this lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease.Methods We compared prospectively serum levels of several biomarkers associated with lung fibrosis in SSc patients (n = 102) compared to healthy subjects (HS) (n = 39). We also performed a longitudinal study in a subgroup of 28 patients analyzing biomarkers variations and pulmonary function tests over a period of 2 years. Furthermore, we performed in vitro analysis to study the impact of Insulin like Growth Factor Binding Protein (IGFBP)-2 on fibrotic activity of human lung fibroblasts.Results Serum levels of IGFBP-1, IGFBP-2, interleukin-8 and matrix metallopeptidase-9 were significantly increased in SSc patients compared to HS while IGF-1 and IGFBP-3 were reduced. The variation of IGFBP-2 between baseline and 2-year follow-up was positively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) at 2-year follow-up (r = 0.6, p < 0.001). Receiver operating characteristic curve analysis enabled us to identify that baseline IGFBP-2 < 105 ng/ml was associated with a better outcome (low risk to display KCO < 70% predicted) at 2-year follow-up (area under the curve = 0.75 at 75% sensibility and 68% specificity, p < 0.05). In vitro functional study showed that IGFBP-2 significantly reduced fibroblast proliferation and pro-fibrotic activity.Conclusions We showed for the first time that serum levels of IGFBP-2 might predict the evolution of SSc-ILD. Baseline IGFBP-2 above 105 ng/ml might be a prognostic factor of alveolo-capillary dysfunction.

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“…IGF binding protein 1 (IGFBP1) also regulates the signals generated by adhesion receptors and growth receptors, thereby regulating the cellular processes. In addition, the cross talk between insulin-like growth receptor and β1-integrin receptor has been reported to play an important role in the prolidase activity and collagen biosynthesis [ 102 ], which together with IGFBP1 and 2 and their proteolytic fragments, have been shown to improve tissue repair process under inflammatory conditions, by acting upon the pathways that control proliferation and migration of HDFs [ 121 ].…”

Section: Signaling Pathways Of Cellular Interactions Within Skinmentioning

confidence: 99%

Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging

Gaur

Dobke

Lunyak

2017

IJMS

157

124

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Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology.

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Effects of IGFBP-1 and IGFBP-2 and their fragments on migration and IGF-induced proliferation of human dermal fibroblasts

Cited by 32 publications

References 38 publications

Transcriptome profiling identifies regulators of pathogenesis in collagen VI related muscular dystrophy

Transcriptome profiling identifies regulators of pathogenesis in collagen VI related muscular dystrophy

Serum IGFBP-2 in Systemic Sclerosis as a Protective Factor of Lung Dysfunction

Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging

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