ABSTRACT
The development of biological macromolecule hydrogel dressings with fatigue resistance, sufficient mechanical strength, and versatility in clinical treatment is critical for accelerating full-thickness healing of skin wounds. Therefore, in this study, multifunctional, biological macromolecule hydrogels based on a recombinant type I collagen/chitosan scaffold incorporated with a metal-polyphenol structure were fabricated to accelerate wound healing. The resulting biological macromolecule hydrogel possesses sufficient mechanical strength, fatigue resistance, and healing properties, including antibacterial, antioxygenic, self-healing, vascularization, hemostatic, and adhesive abilities. Chitosan and recombinant type I collagen formed the scaffold network, which was the first covalent crosslinking network of the hydrogel. The second physical crosslinking network comprised the coordination of a metal-polyphenol structure, i.e., Cu2+ with the catechol group of dopamine methacrylamide (DMA) and stacking of DMA benzene rings. Double-crosslinked networks are interspersed and intertwined in the hydrogel to reduce the mechanical strength and increase its fatigue resistance, making it more suitable for clinical applications. Moreover, the biological macromolecule hydrogel can continuously release Cu2+, which provides strong antibacterial and vascularization properties. An in vivo full-thickness skin defect model confirmed that multifunctional, biological macromolecule hydrogels based on a recombinant type I collagen/chitosan scaffold incorporated with a metal-polyphenol structure can facilitate the formation of granulation tissue and collagen deposition for a short period to promote wound healing. This study highlights that this biological macromolecule hydrogel is a promising acute wound-healing dressing for biomedical applications.
ABSTRACT
The Lin-11, Isl-1, and Mec-3 (LIM) homeodomain transcription factor Isl-1 has been reported to be involved in pituitary development in the early stages of mouse embryogenesis. Our recent studies have shown that Isl-1 is mainly located in the pituitary gonadotropes throughout pituitary development and persists to adulthood. We still do not know the physiological functions of Isl-1 expression and its related mechanisms in the pituitary gland. The aim of the present study was to examine the hypothesis that Isl-1 is involved in regulating pituitary gonadotropin hormone (FSH/LH) production by activating FSHß and LHß gene expressions. We have shown that Isl-1 activates FSHß and LHß subunit promoters and endogenous gene transcription in LßT2 cells. In addition, Isl-1 overexpression significantly increased FSH synthesis and secretion but not LH. The actions of Isl-1 were not observed when the homeodomain or LIM1 domains are mutated. This demonstrates that Isl-1 induction of FSHß and LHß is by both direct and indirect binding of Isl-1 to DNA sequences. Furthermore, Isl-1 expressional level was up-regulated in LßT2 cells after exposure to GnRH, activin, and leptin. However, RNA interference-induced knockdown of Isl-1 significantly reduced the effect of leptin but did not obviously influence the stimulating effects of GnRH and activin on LH and FSH production. In conclusion, the results demonstrate that the LIM-homeodomain transcription factor Isl-1 functions to increase FSHß/LHß gene transcription, and mediates the effects of leptin on gonadotropin synthesis.
Subject(s)
Follicle Stimulating Hormone, beta Subunit/genetics , Gonadotropins/biosynthesis , Homeodomain Proteins/physiology , Leptin/pharmacology , Luteinizing Hormone, beta Subunit/genetics , Animals , Base Sequence , Cells, Cultured , Follicle Stimulating Hormone, beta Subunit/metabolism , Gene Expression/drug effects , Gonadotrophs/drug effects , Gonadotrophs/metabolism , Gonadotropins/genetics , Gonadotropins/metabolism , Homeodomain Proteins/metabolism , Humans , LIM-Homeodomain Proteins , Leptin/metabolism , Luteinizing Hormone, beta Subunit/metabolism , Male , Mice , Molecular Sequence Data , Promoter Regions, Genetic/drug effects , Promoter Regions, Genetic/genetics , Protein Binding/drug effects , Transcription Factors , Up-Regulation/drug effects , Up-Regulation/geneticsABSTRACT
The aims of the present study were to detect the ontogeny of estrogen receptor (ERalpha and ERbeta) and androgen receptor (AR) expressions and their co-localization with Islet-1 in the developing dorsal root ganglia (DRG) of sheep fetuses by immunohistochemistry. From the single staining results, the ERalpha immunoreactivity (ERalpha-ir), ERbeta immunoreactivity (ERbeta-ir) and AR immunoreactivity (AR-ir) was first detected at days 90, 120 and 90 of gestation, respectively. From days 90 to 120, ERalpha and AR were consistently detected in the nuclei of DRG neurons and the relative percentage (approximately 60%) of ERalpha-ir or AR-ir cells did not change significantly. Moreover, there was no change in ERalpha expression, while a dramatic loss of AR expression was observed at birth. From day 120 of gestation to birth, very few neurons (approximately 8%) showed nuclear ERbeta immunoreactivity. The dual staining results showed that Islet-1 was co-localized with ERalpha, ERbeta or AR in the nuclei of DRG neurons with various frequencies, and over 70% ERalpha-ir, ERbeta-ir or AR-ir cells contained Islet-1. These results imply that ERs, AR and Islet-1 may be important in regulating the differentiation and functional maintenance of some phenotypes of DRG neurons after mid-gestation in the sheep fetus.