Hepatoma-Derived Growth Factor (HDGF): A New Heparin-Binding Growth Factor Identified in Leiomyomas and Normal Myometrium

AbstractObjectivesTo study the expression of growth factors in the regulation of tissue repair after peritoneal damage tissue response to peritoneal damage.MethodsExperimental study in 35 male Wistar rats determining the evolution over time of the tissue response to aseptic peritoneal damage. A standardized bowel and peritoneal lesions were created in the right lower quadrant by laparotomy. Then, tissular expression of growth factors was evaluated by multiplex polymerase chain reaction at seven timepoints between 6 h and 30 days, postoperatively.ResultsTissular responses of granulocyte-stimulating factors (Csf2, Csf3), connective tissue growth factor (Ctgf), epidermal growth factors and receptor (Egf, Egfr), fibroblast growth factors (Fgf2, 7 and 10), heparin binding EGF-like growth factor (Hbegf), hepatocyte growth factor (Hgf), insulin-like growth factor-1 (Igf1), mitogenic transforming growth factors (Tgfa, Tgfb1, Tgfbr3), and vascular endothelial growth factor A (Vegfa) were biphasic with a first expression peak at day 3, followed by a more pronounced peak at day 14.ConclusionsWe observed a long-lasting, widespread response of tissular growth factors for at least two weeks after peritoneal damage. To be clinically effective, the prophylaxis of postoperative adhesions might be needed for an extended period of time.

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Heparin-binding epidermal growth factor-like growth factor is an autocrine growth factor for human keratinocytes.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)32127-0 ◽

1994 ◽

Vol 269 (31) ◽

pp. 20060-20066 ◽

Cited By ~ 5

Author(s):

K. Hashimoto ◽

S. Higashiyama ◽

H. Asada ◽

E. Hashimura ◽

T. Kobayashi ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Human Keratinocytes ◽

Heparin Binding ◽

Autocrine Growth ◽

Autocrine Growth Factor ◽

Epidermal Growth

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Dual Action of Sulfated Hyaluronan on Angiogenic Processes in Relation to Vascular Endothelial Growth Factor-A

Scientific Reports ◽

10.1038/s41598-019-54211-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Linda Koehler ◽

Gloria Ruiz-Gómez ◽

Kanagasabai Balamurugan ◽

Sandra Rother ◽

Joanna Freyse ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Computational Study ◽

Treatment Strategies ◽

Vascular Endothelial ◽

Heparin Binding ◽

Heparin Binding Domain ◽

Dual Action ◽

Prospective Application ◽

Endothelial Growth Factor

AbstractPathological healing characterized by abnormal angiogenesis presents a serious burden to patients’ quality of life requiring innovative treatment strategies. Glycosaminoglycans (GAG) are important regulators of angiogenic processes. This experimental and computational study revealed how sulfated GAG derivatives (sGAG) influence the interplay of vascular endothelial growth factor (VEGF)165 and its heparin-binding domain (HBD) with the signaling receptor VEGFR-2 up to atomic detail. There was profound evidence for a HBD-GAG-HBD stacking configuration. Here, the sGAG act as a “molecular glue” leading to recognition modes in which sGAG interact with two VEGF165-HBDs. A 3D angiogenesis model demonstrated the dual regulatory role of high-sulfated derivatives on the biological activity of endothelial cells. While GAG alone promote sprouting, they downregulate VEGF165-mediated signaling and, thereby, elicit VEGF165-independent and -dependent effects. These findings provide novel insights into the modulatory potential of sGAG derivatives on angiogenic processes and point towards their prospective application in treating abnormal angiogenesis.

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