Growth factors最新文献

FGF2 is a potent stimulator of vascular growth; however, even with a deficiency of FGF2 (Fgf2-/-), developmental vessel growth or ischaemia-induced revascularization still transpires. It remains to be elucidated as to what function, if any, FGF2 has during ischaemic injury. Wildtype (WT) or Fgf2-/- mice were subjected to hindlimb ischaemia for up to 42 days. Limb function, vascular growth, inflammatory- and angiogenesis-related proteins, and inflammatory cell infiltration were assessed in sham and ischaemic limbs at various timepoints. Recovery of ischaemic limb function was delayed in Fgf2-/- mice. Yet, vascular growth response to ischaemia was similar between WT and Fgf2-/- hindlimbs. Several angiogenesis- and inflammatory-related proteins (MCP-1, CXCL16, MMPs and PAI-1) were increased in Fgf2-/- ischaemic muscle. Neutrophil or monocyte recruitment/infiltration was elevated in Fgf2-/- ischaemic muscle. In summary, our study indicates that loss of FGF2 induces a pro-inflammatory microenvironment in skeletal muscle which exacerbates ischaemic injury and delays functional limb use.

Heparin-binding EGF-like growth factor (HB-EGF) is involved in atherosclerosis progression. We investigated association between plasma HB-EGF levels and lipid, oxidative stress and inflammatory biomarkers in pediatric patients with type 1 diabetes mellitus (T1DM). Levels of HB-EGF, high-sensitive C-reactive protein (hsCRP), prooxidant-antioxidant balance (PAB), total antioxidant status (TAS), oxidized low-density lipoproteins (oxLDL), metabolic control and serum lipid parameters and paraoxonase 1 (PON1) activity were determined in 74 patients and 40 controls. In comparison to controls, patients had significantly higher levels (p < 0.01) of HB-EGF, hsCRP, PAB and oxLDL particles (p < 0.001), but lower levels of TAS and PON1 activity. In T1DM group, HB-EFG levels were positively associated with hsCRP, PAB and oxLDL levels. hsCRP and oxLDL levels were independent predictors of HB-EGF concentration. We demonstrated that oxidative modifications of LDL particles and low-grade inflammation are main determinants of increased plasma HB-EGF levels, which indicates an interactive role of oxidative stress, dyslipidemia and inflammation.

Quercetin on wounds could be favorable for healing based on its variety of biological effects. Eighty wounded rats were divided into four groups i.e. dimethyl sulfoxide, 0.03% quercetin, 0.1% quercetin, and 0.3% quercetin-treated. Different treatments were topically applied for 20 days. Quercetin (0.3%) caused the fastest wound closure and markedly improved the oxidative stress. Quercetin treatment increased the expressions of IL-10, VEGF, TGF-β₁, CD31, α-SMA, PCNA, and GAP-43, and decreased the expressions of TNF-α. Early infiltration of inflammatory cells and formation of good quality granulation tissue dominated by fibroblast proliferation, angiogenesis, and collagen deposition in quercetin treated groups was also evident. All these effects were more pronounced at 0.3% quercetin concentration. The earliest regeneration of epithelial layer was also observed in 0.3% quercetin-treated wounds. In conclusion, 0.3% quercetin accelerates wound healing efficiently by modulating antioxidant system of wound, cytokines, growth factors, other proteins and cells involved in healing.

The present study aimed to investigate the protective role of sirtuin 1 (SIRT1) and oxygen regulated protein 150 (ORP150) in a rat COPD model by inducing changes in ER stress and apoptosis. We separated 48 Sprague Dawley (SD) rats into four groups randomly: the control group, resveratrol group, COPD group and the resveratrol intervention group. Rats were challenged with cigarette smoke and lipopolysaccharide with resveratrol (a selective activator of SIRT1). The lung functions of the rats were measured and recorded. The expression levels of SIRT1 and ORP150 in lung tissues were examined by western blot and RTq PCR. The expression levels of the ER stress apoptosis-associated protein were determined .The apoptotic level of lung tissues was analyzed. The results suggest that SIRT1 attenuated apoptosis and ER stress in the lung tissues of rats with COPD. During this process, a positive correlation was identified between SIRT1 and ORP150.

Cyclosporine-A (CsA) is a widely used immunosuppressant. In this study, we explore the pathway through which CsA suppressed the Porphyromonas gingivalis lipopolysaccharide (P.g-LPS)-induced increase in matrix metalloproteinase (MMP) activities in co-cultured human gingival fibroblasts (HGFs) and THP-1 monocytes. In the co-culture, we found that CsA inhibited the expression of cyclophilin A (CyPA), CD147 and the activities of MMPs, which were all induced by P.g-LPS. We also found that P.g-LPS and recombinant human CyPA increased activation of ERK1/2 and IκB (an NF-κB inhibitory protein), but CsA and the anti-CD147 antibody significantly inhibited these effects. Taken together, CsA in the presence of P.g-LPS might suppress MMP activities by blocking the CyPA/CD147 interaction that results in the inhibition of ERK1/2 and NF-κB signaling by interfering with the phosphorylation of ERK1/2 and IκB.

Novel advances for cardiovascular diseases (CVDs) include regenerative approaches for fibrosis, hypertrophy, and neoangiogenesis. Studies indicate that growth factor (GF) signaling could promote heart repair since most of the evidence is derived from preclinical models. Observational studies have evaluated GF serum/plasma levels as feasible biomarkers for risk stratification of CVDs. Noteworthy, two clinical interventional published studies showed that the administration of growth factors (GFs) induced beneficial effect on left ventricular ejection fraction (LVEF), myocardial perfusion, end-systolic volume index (ESVI). To date, large scale ongoing studies are in Phase I-II and mostly focussed on intramyocardial (IM), intracoronary (IC) or intravenous (IV) administration of vascular endothelial growth factor (VEGF) and fibroblast growth factor-23 (FGF-23) which result in the most investigated GFs in the last 10 years. Future data of ongoing randomized controlled studies will be crucial in understanding whether GF-based protocols could be in a concrete way effective in the clinical setting.

During the period of lactation, there is extensive growth and development of the mammary gland in order to fulfil the increased demands of milk for the growing infant. Angiogenesis plays a key role in alveolar development and facilitates optimal milk production. Vascular endothelial growth factor (VEGF) is one of the key growth factors regulating angiogenesis in mammary gland. Apart from VEGF, neurotrophins are also known to regulate angiogenesis through direct or indirect mechanisms. Few studies have demonstrated mRNA levels of neurotrophins and their receptors in mammary gland both in humans and rodents. A cross talk between VEGF and neurotrophins has been described in placental development. The enteric and central nervous system are not fully developed at birth, making it imperative to have appropriate levels of angiogenic factors and neurotrophins during postnatal period. The current review summarises studies which describe the role of neurotrophins and angiogenic factors in the mammary gland development.

As the largest organ of the body, human skin is multifunctional and enjoys two layers, the epidermis and the dermis, the separation of which is performed by a basement membrane zone. Skin protects the body against mechanical forces and infections. Skin wounds represent large and growing challenges to the healthcare systems globally. Skin wound healing, as a protective shield for the body against the external environment, includes interactions among cell types, the neurovascular system, cytokines, and matrix remodeling. Growth factors (GFs) affect the microenvironment of the wound, and cause rises in cell differentiation, proliferation, and migration. Administrating exogenous GFs has revealed potential in enhancing wound healing outcomes. The use of human GFs in the field of wound healing is becoming gradually more interesting, because of the low-invasive techniques required for their use. Reviewed here are the literatures on the healing of skin wounds with emphasize on the role of GFs and their future prospects, containing profits, and probable long-standing side effects accompanied with their use.

Trophic factors are naturally produced by different tissues that participate in several functions such as the intercellular communication, in the development, stability, differentiation and regeneration at the cellular level. Specifically, in the case of spinal injuries, these factors can stimulate neuronal recovery. They are applied both in experimental models and in clinical trials in patients. The trophic factors analysed in this review include gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), growth hormone (GH), melatonin, oestrogens, the family of fibroblast growth factors (FGFs), the family of neurotrophins and the glial cell-derived neurotrophic factor (GDNF). There are some trophic (neurotrophic) factors that already been tested in patients with spinal cord injury (SCI), but only shown partial recovery effect. It is possible that, the administration of these trophic factors together with physical rehabilitation, act synergistically and, therefore, significantly improve the quality of life of patients with SCI.