Crosstalk Between PDGF and IGF-I Receptors in Rat Liver Myofibroblasts: Implication for Liver Fibrogenesis

Novosyadlyy, Ruslan; Dudas, J.; Samoylenko, Anatoly; Ramadori, Giuliano; Scharf, JG

doi:10.1055/s-2005-861600

Cited by 3 publications

(4 citation statements)

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“…The discordant IGFBP-2 and IGFBP-3 levels in TPSC may thus in a paracrine fashion be involved in enhancing pancreatic cancer cell growth by stabilizing IGF-I levels in the local tumor area as well as enhancing the activity of IGF/PI3K pathway. IGF-I has been demonstrated as an important mitogen for liver myofibroblasts [30]. IGF-I is also known to stimulate both pancreatic cancer cell proliferation and motility [31].…”

Section: Discussionmentioning

confidence: 99%

Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I

Rosendahl

Gundewar

Hilmersson

et al. 2015

Experimental Cell Research

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Pancreatic stellate cells (PSCs) play a key role in the dense desmoplastic stroma associated with pancreatic ductal adenocarcinoma. Studies on human PSCs have been minimal due to difficulty in maintaining primary PSC in culture. We have generated the first conditionally immortalized human non-tumor (NPSC) and tumor-derived (TPSC) pancreatic stellate cells via transformation with the temperature-sensitive SV40 large T antigen and human telomerase (hTERT). These cells proliferate at 33°C. After transfer to 37°C, the SV40LT is switched off and the cells regain their primary PSC phenotype and growth characteristics. NPSC contained cytoplasmic vitamin A-storing lipid droplets, while both NPSC and TPSC expressed the characteristic markers αSMA, vimentin, desmin and GFAP. Proteome array analysis revealed that of the 55 evaluated proteins, 27 (49%) were upregulated ≥3-fold in TPSC compared to NPSC, including uPA, pentraxin-3, endoglin and endothelin-1. Two insulin-like growth factor binding proteins (IGFBPs) were inversely expressed. Although discordant IGFBP-2 and IGFBP-3 levels, IGF-I was found to stimulate proliferation of both NPSC and TPSC. Both basal and IGF-I stimulated motility was significantly enhanced in TPSC compared to NPSC. In conclusion, these cells provide a unique resource that will facilitate further study of the active stroma compartment associated with pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I

Rosendahl

Gundewar

Hilmersson

et al. 2015

Experimental Cell Research

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“…Another challenge is to identify major convergent points in the cell where interactions between growth factors induced signalling might occur (31). In doing so, it may be possible to ascertain transcriptional regulatory networks likely to control dynamics of receptors' up-and down-regulation (32,33).…”

Section: Discussionmentioning

confidence: 99%

Fibroblastic response to treatment with different preparations rich in growth factors

et al. 2009

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“…Activation of the insulin‐like growth factor‐I receptor (IGF‐IR) by binding of IGF‐I and IGF‐2 plays important roles in cell proliferation, survival and inhibition of apoptosis . The IGF‐1/IGF‐IR pathway has been implicated in a number of fibrotic diseases, such as renal fibrosis in IgA nephropathy, fibroproliferative acute respiratory distress syndrome and rat liver fibrogenesis . Moreover, previous studies have demonstrated that IGF and IGF‐IR are involved in keloid and HS …”

Section: Introductionmentioning

confidence: 99%

“…7,8 The IGF-1/IGF-IR pathway has been implicated in a number of fibrotic diseases, such as renal fibrosis in IgA nephropathy, fibroproliferative acute respiratory distress syndrome and rat liver fibrogenesis. [9][10][11] Moreover, previous studies have demonstrated that IGF and IGF-IR are involved in keloid and HS. [12][13][14][15][16] Recently, several studies reported that IGF-IR was overexpressed in keloid fibroblasts, which was shown to enhance the invasive activity of fibroblasts and to make fibroblasts resistant to ceramide-induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Expression of insulin‐like growth factor‐1 receptor in keloid and hypertrophic scar

Tang

Guo

et al. 2014

Clin Exp Dermatol

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BackgroundKeloid and hypertrophic scar (HS) are two pathological forms of excessive dermal fibrosis, which are due to aberrant wound-healing responses. Accumulating evidence suggests that aberrant activity of growth factors and increased numbers of growth factor receptors play an important role in the formation of pathological scar.AimWe examined the expression level of insulin-like growth factor-1 receptor (IGF-IR) in keloid, HS and normal skin.MethodsIGF-IR expression was analyzed by immunohistochemistry, real-time PCR and western blotting on tissues and fibroblasts from 30 patients, comprising 10 patients with keloid and 20 with HS (10 with immature and 10 with mature HS), and from 10 age-matched and sex-matched healthy controls.ResultsImmunoreactivity to IGF-IR was found in dermal fibroblasts of keloid (90%), immature HS, (80%) and mature HS (30%), but not in normal skin. There was no statistically significant difference in immunoreactivity scores between keloid and immature HS, but there was a significant difference (P < 0.01) between mature and immature HS. Real-time PCR and western blot analysis confirmed that there was high expression of IGF-IR in keloid and immature HS fibroblasts, but not in mature HS or normal skin fibroblasts. IGF-IR was expressed in the overlying epidermis, and there was no significant difference between the groups.ConclusionsIGF-IR may be involved in the pathogenesis of keloid and HS. Given that IGF-IR are predominantly expressed on dermal fibroblasts, targeting of IGF-IR in fibroblasts may be of benefit to prevent scarring.

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Crosstalk Between PDGF and IGF-I Receptors in Rat Liver Myofibroblasts: Implication for Liver Fibrogenesis

Cited by 3 publications

References 0 publications

Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I

Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I

Fibroblastic response to treatment with different preparations rich in growth factors

Expression of insulin‐like growth factor‐1 receptor in keloid and hypertrophic scar

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