Browse
Submit Data
Databases
API
Help

Dataset Information

40 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuronal PAS Domain 2 (Npas2)-Deficient Fibroblasts Accelerate Skin Wound Healing and Dermal Collagen Reconstruction.

ABSTRACT: The circadian clock, which consists of endogenous self-sustained and cell-autonomous oscillations in mammalian cells, is known to regulate a wide range of peripheral tissues. The unique upregulation of a clock gene, neuronal PAS domain protein 2 (Npas2), observed along with fibroblast aging prompted us to investigate the role of Npas2 in the homeostasis of dermal structure using in vivo and in vitro wound healing models. Time-course healing of a full-thickness skin punched wound exhibited significantly faster wound closure in Npas2-/- mice than wild-type (WT) C57Bl/6J mice. Dorsal skin fibroblasts isolated from WT, Npas2+/-, and Npas2-/- mice exhibited consistent profiles of core clock gene expression except for Npas2 and Per2. In vitro behavioral characterizations of dermal fibroblasts revealed that Npas2-/- mutation was associated with increased proliferation, migration, and cell contraction measured by floating collagen gel contraction and single-cell force contraction assays. Npas2 knockout fibroblasts carrying sustained the high expression level of type XII and XIV FAICT collagens and synthesized dermis-like thick collagen fibers in vitro. Confocal laser scanning microscopy demonstrated the reconstruction of dermis-like collagen architecture in the wound healing area of Npas2-/- mice. This study indicates that the induced Npas2 expression in fibroblasts may interfere with skin homeostasis, wound healing, and dermal tissue reconstruction, providing a basis for novel therapeutic target and strategy. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.

SUBMITTER: Sasaki H

PROVIDER: S-EPMC6733676 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Non pharmacological high-intensity ultrasound treatment of human dermal fibroblasts to accelerate wound healing.

Project description:Inspired by the effectiveness of low-intensity ultrasound on tissue regeneration, we investigated the potential effect of short-term high-intensity ultrasound treatment for acceleration of wound healing in an in vitro wound model and dermal equivalent, both comprising human dermal fibroblasts. Short-term ultrasound of various amplitudes significantly increased the proliferation and migration of fibroblasts and subsequently increased the production of the extracellular matrix components fibronectin and collagen type I, both of which are important for wound healing and are secreted by fibroblasts. In addition, ultrasound treatment increased the contraction of a fibroblast-embedded three-dimensional collagen matrix, and the effect was synergistically increased in the presence of TGF-β. RNA-sequencing and bioinformatics analyses revealed changes in gene expression and p38 and ERK1/2 MAPK pathway activation in the ultrasound-stimulated fibroblasts. Our findings suggest that ultrasound as a mechanical stimulus can activate human dermal fibroblasts. Therefore, the activation of fibroblasts using ultrasound may improve the healing of various types of wounds and increase skin regeneration.

| S-EPMC7844265 | biostudies-literature

Human collagen alpha-2 type I stimulates collagen synthesis, wound healing, and elastin production in normal human dermal fibroblasts (HDFs).

Project description:Skin aging appears to be the result of overlapping intrinsic (including genetic and hormonal factors) and extrinsic (external environment including chronic light exposure, chemicals, and toxins) processes. These factors cause decreases in the synthesis of collagen type I and elastin in fibroblasts and increases in the melanin in melanocytes. Collagen Type I is the most abundant type of collagen and is a major structural protein in human body tissues. In previous studies, many products containing collagen derived from land and marine animals as well as other sources have been used for a wide range of purposes in cosmetics and food. However, to our knowledge, the effects of human collagenderived peptides on improvements in skin condition have not been investigated. Here we isolate and identify the domain of a human COL1A2-derived protein which promotes fibroblast cell proliferation and collagen type I synthesis. This human COL 1A2-derived peptide enhances wound healing and elastin production. Finally, the human collagen alpha-2 type I-derived peptide (SMM) ameliorates collagen type I synthesis, cell proliferation, cell migration, and elastin synthesis, supporting a significant anti-wrinkle effect. Collectively, these results demonstrate that human collagen alpha-2 type I-derived peptides is practically accessible in both cosmetics and food, with the goal of improving skin condition. [BMB Reports 2020; 53(10): 539-544].

| S-EPMC7607150 | biostudies-literature

Combination of Glycinamide and Ascorbic Acid Synergistically Promotes Collagen Production and Wound Healing in Human Dermal Fibroblasts.

Project description:The purpose of this study is to present a novel strategy to enhance collagen production in cells. To identify amino acid analogs with excellent collagen production-enhancing effects, human dermal fibroblasts (HDFs) were treated with 20 kinds of amidated amino acids and 20 kinds of free amino acids, individually at 1 mM. The results showed that glycinamide enhanced collagen production (secreted collagen level) most effectively. Glycine also enhanced collagen production to a lesser degree. However, other glycine derivatives, such as N-acetyl glycine, N-acetyl glycinamide, glycine methyl ester, glycine ethyl ester, and glycyl glycine, did not show such effects. Glycinamide increased type I and III collagen protein levels without affecting COL1A1 and COL3A1 mRNA levels, whereas transforming growth factor-β1 (TGF-β1, 10 ng mL-1) increased both mRNA and protein levels of collagens. Ascorbic acid (AA, 1 mM) increased COL1A1 and COL3A1 mRNA and collagen I protein levels. Unlike TGF-β1, AA and glycinamide did not increase the protein level of α-smooth muscle actin, a marker of differentiation of fibroblasts into myofibroblasts. The combination of AA and glycinamide synergistically enhanced collagen production and wound closure in HDFs to a level similar to that in cells treated with TGF-β1. AA derivatives, such as magnesium ascorbyl 3-phosphate (MAP), 3-O-ethyl ascorbic acid, ascorbyl 2-O-glucoside, and ascorbyl tetraisopalmitate, enhanced collagen production, and the mRNA and protein levels of collagens at 1 mM, and their effects were further enhanced when co-treated with glycinamide. Among AA derivatives, MAP had a similar effect to AA in enhancing wound closure, and its effect was further enhanced by glycinamide. Other AA derivatives had different effects on wound closure. This study provides a new strategy to enhance cell collagen production and wound healing using glycinamide in combination with AA.

| S-EPMC9138459 | biostudies-literature

Therapeutic downregulation of <i>neuronal PAS domain 2</i> (<i>Npas2</i>) promotes surgical skin wound healing.

Project description:Attempts to minimize scarring remain among the most difficult challenges facing surgeons, despite the use of optimal wound closure techniques. Previously, we reported improved healing of dermal excisional wounds in circadian clock neuronal PAS domain 2 (Npas2)-null mice. In this study, we performed high-throughput drug screening to identify a compound that downregulates Npas2 activity. The hit compound (Dwn1) suppressed circadian Npas2 expression, increased murine dermal fibroblast cell migration, and decreased collagen synthesis in vitro. Based on the in vitro results, Dwn1 was topically applied to iatrogenic full-thickness dorsal cutaneous wounds in a murine model. The Dwn1-treated dermal wounds healed faster with favorable mechanical strength and developed less granulation tissue than the controls. The expression of type I collagen, Tgfβ1, and α-smooth muscle actin was significantly decreased in Dwn1-treated wounds, suggesting that hypertrophic scarring and myofibroblast differentiation are attenuated by Dwn1 treatment. NPAS2 may represent an important target for therapeutic approaches to optimal surgical wound management.

| S-EPMC8789286 | biostudies-literature

Effects of cardiotonic steroids on dermal collagen synthesis and wound healing.

Project description:We previously reported that cardiotonic steroids stimulate collagen synthesis by cardiac fibroblasts in a process that involves signaling through the Na-K-ATPase pathway (Elkareh et al. Hypertension 49: 215-224, 2007). In this study, we examined the effect of cardiotonic steroids on dermal fibroblasts collagen synthesis and on wound healing. Increased collagen expression by human dermal fibroblasts was noted in response to the cardiotonic steroid marinobufagenin in a dose- and time-dependent fashion. An eightfold increase in collagen synthesis was noted when cells were exposed to 10 nM marinobufagenin for 24 h (P < 0.01). Similar increases in proline incorporation were seen following treatment with digoxin, ouabain, and marinobufagenin (10 nM x 24 h, all results P < 0.01 vs. control). The coadministration of the Src inhibitor PP2 or N-acetylcysteine completely prevented collagen stimulation by marinobufagenin. Next, we examined the effect of digoxin, ouabain, and marinobufagenin on the rate of wound closure in an in vitro model where human dermal fibroblasts cultures were wounded with a pipette tip and monitored by digital microscopy. Finally, we administered digoxin in an in vivo wound healing model. Olive oil was chosen as the digoxin carrier because of a favorable partition coefficient observed for labeled digoxin with saline. This application significantly accelerated in vivo wound healing in rats wounded with an 8-mm biopsy cut. Increased collagen accumulation was noted 9 days after wounding (both P < 0.01). The data suggest that cardiotonic steroids induce increases in collagen synthesis by dermal fibroblasts, as could potentially be exploited to accelerate wound healing.

| S-EPMC2494826 | biostudies-literature

Type II Collagen from Cartilage of Acipenser baerii Promotes Wound Healing in Human Dermal Fibroblasts and in Mouse Skin.

Project description:Type II collagen is an important component of cartilage; however, little is known about its effect on skin wound healing. In this study, type II collagen was extracted from the cartilage of Acipenser baerii and its effect on in vitro and in vivo wound healing was compared to type I collagen derived from tilapia skin. Sturgeon cartilage collagen (SCC) was composed of α1 chains and with a thermal denaturation (Td) at 22.5 and melting temperature (Tm) at 72.5 °C. Coating SCC potentiated proliferation, migration, and invasion of human dermal fibroblast adult (HDFa) cells. Furthermore, SCC upregulated the gene expression of extracellular matrix (ECM) components (col Iα1, col IIIα1, elastin, and Has2) and epithelial-mesenchymal transition (EMT) molecules (N-cadherin, Snail, and MMP-1) in HDFa. Pretreatment with Akt and mitogen-activated protein kinase (MAPK) inhibitors significantly attenuated the HDFa invasion caused by SCC. In mice, the application of SCC on dorsal wounds effectively facilitated wound healing as evidenced by 40-59% wound contraction, whereas the untreated wounds were 18%. We observed that SCC reduced inflammation, promoted granulation, tissue formation, and ECM deposition, as well as re-epithelialization in skin wounds. In addition, SCC markedly upregulated the production of growth factors in the dermis, and dermal and subcutaneous white adipose tissue; in contrast, the administration of tilapia skin collagen (TSC) characterized by typical type I collagen was mainly expressed in the epidermis. Collectively, these findings indicate SCC accelerated wound healing by targeting fibroblast in vitro and in vivo.

| S-EPMC7601416 | biostudies-literature

Non-adenine based purines accelerate wound healing.

Project description:Wound healing is a complex sequence of cellular and molecular processes that involves multiple cell types and biochemical mediators. Several growth factors have been identified that regulate tissue repair, including the neurotrophin nerve growth factor (NGF). As non-adenine based purines (NABPs) are known to promote cell proliferation and the release of growth factors, we investigated whether NABPs had an effect on wound healing. Full-thickness, excisional wound healing in healthy BALB/c mice was significantly accelerated by daily topical application of NABPs such as guanosine (50% closure by days 2.5-2.8). Co-treatment of wounds with guanosine plus anti-NGF reversed the guanosine-promoted acceleration of wound healing, indicating that this effect of guanosine is mediated, at least in part, by NGF. Selective inhibitors of the NGF-inducible serine/threonine protein kinase (protein kinase N), such as 6-methylmercaptopurine riboside abolished the acceleration of wound healing caused by guanosine, confirming that activation of this enzyme is required for this effect of guanosine. Treatment of genetically diabetic BKS.Cg-m+/+lepr db mice, which display impaired wound healing, with guanosine led to accelerated healing of skin wounds (25% closure by days 2.8-3.0). These results provide further confirmation that the NABP-mediated acceleration of cutaneous wound healing is mediated via an NGF-dependent mechanism. Thus, NABPs may offer an alternative and viable approach for the treatment of wounds in a clinical setting.

| S-EPMC2096660 | biostudies-other

The Effectiveness of Porcine Dermal Collagen (Permacol(®)) on Wound Healing in the Rat Model.

Project description:Porcine acellular dermal collagen (PDC), which is a biological material derived from processing porcine dermis, has already been used for urologic, gynecologic, plastic, and general surgery procedures up to now. The aim of this study is to investigate the effectiveness of PDC on wound healing as a dermal substitute in the rat model. Twenty Wistar albino rats were divided into two groups. Standard full-thickness skin defects were created on the back of the rats. In the control group (Group 1), the dressings moisturized with saline were changed daily. In the study group (Group 2), porcine dermal collagen was implanted onto each wound and fixed with 4-0 polypropylene sutures. Contraction percentages of wound areas were calculated on the third, seventh, tenth, and fourteenth days by using the planimetric program. On fourteenth day, the wound areas were excised for histopathological examination, inflammatory scoring, and evaluation of collagen deposition. The study group was superior to the control group in terms of inflammatory scoring, type I/type III collagen ratio, and wound contraction rates. Porcine dermal collagen may be used effectively and safely on full-thickness wounds as a current dermal substitute.

| S-EPMC4692856 | biostudies-literature

Inhibition of β-catenin signalling in dermal fibroblasts enhances hair follicle regeneration during wound healing.

Project description:New hair follicles (HFs) do not form in adult mammalian skin unless epidermal Wnt signalling is activated genetically or within large wounds. To understand the postnatal loss of hair forming ability we monitored HF formation at small circular (2 mm) wound sites. At P2, new HFs formed in back skin, but HF formation was markedly decreased by P21. Neonatal tail also formed wound-associated HFs, albeit in smaller numbers. Postnatal loss of HF neogenesis did not correlate with wound closure rate but with a reduction in Lrig1-positive papillary fibroblasts in wounds. Comparative gene expression profiling of back and tail dermis at P1 and dorsal fibroblasts at P2 and P50 showed a correlation between loss of HF formation and decreased expression of genes associated with proliferation and Wnt/β-catenin activity. Between P2 and P50, fibroblast density declined throughout the dermis and clones of fibroblasts became more dispersed. This correlated with a decline in fibroblasts expressing a TOPGFP reporter of Wnt activation. Surprisingly, between P2 and P50 there was no difference in fibroblast proliferation at the wound site but Wnt signalling was highly upregulated in healing dermis of P21 compared with P2 mice. Postnatal β-catenin ablation in fibroblasts promoted HF regeneration in neonatal and adult mouse wounds, whereas β-catenin activation reduced HF regeneration in neonatal wounds. Our data support a model whereby postnatal loss of hair forming ability in wounds reflects elevated dermal Wnt/β-catenin activation in the wound bed, increasing the abundance of fibroblasts that are unable to induce HF formation.

| S-EPMC4958333 | biostudies-literature

Human dermal fibroblasts derived from oculodentodigital dysplasia patients suggest that patients may have wound-healing defects.

Project description:Oculodentodigital dysplasia (ODDD) is primarily an autosomal dominant human disease caused by any one of over 60 mutations in the GJA1 gene encoding the gap junction protein Cx43. In the present study, wound healing was investigated in a G60S ODDD mutant mouse model and by using dermal fibroblasts isolated from two ODDD patients harboring the p.D3N and p.V216L mutants along with dermal fibroblasts isolated from their respective unaffected relatives. Punch biopsies revealed a delay in wound closure in the G60S mutant mice in comparison to wild-type littermates, and this delay appeared to be due to defects in the dermal fibroblasts. Although both the p.D3N and p.V216L mutants reduced gap junctional intercellular communication in human dermal fibroblasts, immunolocalization studies revealed that Cx43 gap junctions were prevalent at the cell surface of p.D3N expressing fibroblasts but greatly reduced in p.V216L expressing fibroblasts. Mutant expressing fibroblasts were further found to have reduced proliferation and migration capabilities. Finally, in response to TGF?1, mutant expressing fibroblasts expressed significantly less alpha smooth muscle actin suggesting they were inefficient in their ability to differentiate into myofibroblasts. Collectively, our results suggest that ODDD patients may have subclinical defects in wound healing due to impaired function of dermal fibroblasts.

| S-EPMC3180923 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data