Growth factors最新文献

Significant dysregulation of matrix metalloproteinase (MMPs), their tissue inhibitors (TIMPs) and profibrotic cytokines have been reported in hypertrophic cardiomyopathy (HCM) and associated with adverse cardiac remodeling. We aim to investigate the relationship among MMPs, TIMPs, transforming growth factor-β (TGF-β) and amino terminal propeptide of type III procollagen (PIIINP) in HCM patients, and to explore their associations with clinical outcomes. We recruited 46 HCM patients and 49 controls, and measured biomarkers levels using ELISA. Receiver operating characteristic (ROC) analysis revealed the highest diagnostic sensitivity for MMP-2 (93.3%) and specificity for TGF-β (90%). Significant correlations were found between biomarkers and clinical parameters, including interactions between TGF-β and left ventricular mass, MMP-2 and intraventricular septum, PIIINP and maximal wall thickness. We suggest that TGF-β, with the highest specificity and MMP-2, with high sensitivity, may offer significant potential for identifying patients with HCM and serve as useful biomarkers for this disease.

Periodontitis causes severe tissue loss, making predictable regeneration a major challenge. Growth factor-loaded chitosan scaffolds offer a promising, multifunctional approach to enhance tissue regeneration. This review explores their design, optimization, and therapeutic potential, focusing on delivery methods, release kinetics, and biocompatibility. Studies show these scaffolds improve local delivery, sustain growth factor release, and reduce cytotoxicity while offering reinforcement and encouraging cell adhesion. Optimized release kinetics ensure a favorable prognosis, reducing the necessity for recurrent administration. Growth factor-loaded chitosan scaffolds create a biomimetic environment that supports periodontal healing, representing an innovative strategy for advancing periodontal therapy. Further research on scaffold design, growth factor combinations, and long-term outcomes is essential to refine this approach for more effective, predictable regeneration.

IGF1R, a receptor tyrosine kinase, is crucial for cell growth, proliferation, and differentiation. Overexpression of IGF1R is linked to cancer and resistance to therapies, making it a target for drug development. Previously, we identified an allosteric binding pocket in IGF1R, which could be exploited for the development of IGF1R specific small molecule inhibitors. A recent study linked M1054I variant to growth defects and microcephaly. In this study, we functionally characterized M1054I to assess its effects on kinase activity, downstream signaling, and receptor structure. Replacing methionine with isoleucine at position 1054 leads to complete loss of kinase activity. Consequently, activation of downstream signaling molecules is significantly reduced in cells carrying the M1054I mutation. Structural analysis reveals that the mutation causes conformational changes in key conserved regions, particularly in the activation loop, compromising IGF1R's structural integrity and function. Additionally, the roles of residues Y987 and K1033 in regulating IGF1R functions were examined.

myocardial ischemia-reperfusion injury (MI/RI) threatens people's lives. Midkine (MDK) has a protective effect against MI/RI. DNA methyltransferase 1 (DNMT1) is closely associated with MI/RI. Mouse cardiomyocytes were isolated to establish a model of myocardial ischemia-reperfusion. Subsequently, the viability, apoptosis, and inflammatory factors of the cardiomyocytes treated under different conditions were measured. Western blotting was employed to examine the expression of related proteins. Chromatin immunoprecipitation (CHIP) and dual-luciferase reporter gene assays were conducted to verify the relationships among the DNMT1, MDK, and Notch2/Hes1 signaling pathways. The expression of MDK was reduced in the MI/RI cell model, while Notch2/Hes1 was activated. Overexpression of MDK mitigated the injury associated with MI/RI. Methylation modification of DNMT1 downregulated MDK, thereby mediating the Notch2/Hes1 pathway. The methylation modification of DNMT1 on MDK regulated the progression of MI/RI. The methylation modification of MDK by DNMT1 likely downregulates the Notch2/Hes1 pathway, thereby influencing MI/RI.

During the formation of hypertrophic scars (HS), there is often a notable abnormal proliferation and differentiation of cells, especially fibroblasts, but it remains ambiguous whether a causal relationship exists between fibroblast growth factor receptors (FGFRs) and hypertrophic scar. This study explored the causal impact of FGFR1, FGFR2, FGFR3, and FGFR4 on HS utilizing a two-sample Mendelian randomization (MR) analyses. The elevated expression of FGFR1 and FGFR 4 emerged as two potential risk factors against HS in the inverse-variance weighted analysis. Conversely, FGFR2 and FGFR3 exhibited no significant causal relationship with hypertrophic scars. Rigorous analyses including assessments of heterogeneity, genetic horizontal pleiotropy, and leave-one-out sensitivity collectively affirmed the stability and reliability of the findings in this study. Taken together, the elevated expression of FGFR1 and FGFR 4 act as two key regulatory factors in preventing the formation of HS and serves as a crucial modulator in impeding scar formation.

GATA proteins have been proposed as regulators of adipogenesis. In particular, GATA2 and GATA3 have been demonstrated to function in preadipocytes, and their behavior in response to extracellular signals allows preadipocytes to transition into adipocytes in mammals. However, few reports have discussed the extracellular stimulators of both GATAs. In this study, we investigated whether growth hormone (GH) acts as an extracellular ligand of both GATAs, with special attention paid to GATA3 expression in adipocytes. GATA3 expression increased at the transcriptional level with STAT5B activation in a dose-dependent manner, and this was reversed by a STAT5-specific inhibitor. Furthermore, we found that the functional STAT5B consensus sequences that function as the binding site in the GATA3 promoter region were located at -117 bp from the transcription starting site. These results suggest that GH induces GATA3 gene expressions via the GHR/JAK/STAT5 pathway to control adipocyte proliferation and differentiation.

Vascular endothelial growth factor (VEGF) plays a crucial role in maintaining renal homeostasis. However, the precise impact of VEGF on ferroptosis in acute kidney injury (AKI) remains incompletely understood. This study aims to investigate the effects of VEGF on ferroptosis in the model of AKI and to elucidate the underlying mechanisms. We used C57BL mice and HK-2 cells to construct sepsis-associated AKI models. We assessed renal function, cell viability, and tissue levels of iron, malondialdehyde (MDA), and glutathione (GSH) in mice. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential, and electron microscopy-detected cellular changes were also measured. Western blotting analyzed key ferroptosis-related proteins (SLC7A11, GPX4) and components of the ERK1/2-NRF2-GPX4 pathway. VEGF treatment significantly reduced oxidative stress by lowering ROS and MDA levels while increasing GSH. Additionally, VEGF165 activated the ERK1/2-NRF2 pathway, mitigating ferroptosis.

Optic nerve (ON) injury leads to retinal ganglion cell (RGC) degeneration and axonal atrophy. Wnt ligands are embryonic growth factors that regulate cellular differentiation and survival. We recently demonstrated that canonical and non-canonical Wnt signaling induces RGC survival and axonal regrowth after optic nerve crush (ONC) injury in mouse. Here, we investigated whether the non-canonical Wnt5a ligand induces pro-regenerative inflammation after ONC. Mice were intravitreally injected with Wnt5a or saline during ONC and retina tissue was collected for QPCR and immunofluorescence. We demonstrated that expression of arginase 1, a marker of anti-inflammatory microglia, was upregulated by Wnt5a in injured retinas, whereas iNOS, a marker of neurotoxic microglia, was suppressed. Wnt5a also induced time-dependent changes in pro-inflammatory genes Gal3, TNFα, P2RY12 and IL-6 and the anti-inflammatory gene IL-27. These results indicate that Wnt5a is an immunomodulatory ligand in the retina after ONC injury.

Systemic inflammatory response syndrome (SIRS) commonly considered as the first step in the sepsis cascade. To evaluate the diagnostic value and potential mechanism of serum MANF in sepsis-associated lung injury (SALI), 15 adult SALI patients and 15 age- and sex-matched SIRS patients were enrolled to measure serum MANF levels by sandwich enzyme-linked immune-sorbent assay and the laboratory indexes including C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) were collected. MANF and IL-6 levels showed significant differences between groups (P < 0.05), and the area under the curve (AUC) values of MANF and IL-6 were 0.822 and 0.815. The combination of MANF with IL-6 exhibited improved predictive accuracy for SALI. Furthermore, we found that there is a protein interaction network between MANF and all of these overlap targets between ferroptosis-related genes (FRGs) and SALI by bioinformatics analysis. MANF could be a promising biomarker for the differential diagnosis of SALI and SIRS.

To identify distinct patterns of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) in girls with central precocious puberty (CPP), and to compare IGF-1 and IGFBP-3 levels in patients with CPP and precocious thelarche (PT).

A literature search of PubMed, Embase, and Scopus databases was done to identify observational studies. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the studies. Pooled weighted mean difference (WMD) and 95% confidence intervals (CI) were reported.

Fourteen studies were included. As opposed to age-matched or similar-aged pre-pubertal girls, patients with CPP had significantly higher levels of IGF-1 and IGFBP-3. CPP was associated with higher levels of IGF-1 approaching statistical significance but similar levels of IGFBP-3 compared to PT.

Distinct hormonal patterns, such as elevated IGF-1 and IGFBP-3, were identified in patients with CPP, suggesting a potential diagnostic value of IGF-1 and IGFBP-3 levels.