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Results for “Human dermal fibroblasts”

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At least 19 recordsLinked to original sources
PubMed2026

Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway.

BACKGROUND: Tranexamic acid (TXA) is widely used for pigmentary disorders, but its anti-ageing potential remains unclear. This study aimed to evaluate whether topical 3% TXA improves early periorbital wrinkles in women with facial melasma and to investigate whether TXA protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. METHODS: Fifty women with melasma were randomized to 3% TXA serum plus moisturizer or moisturizer alone for 8 weeks, with follow-up to week 12. Periorbital wrinkles were graded using a modified Fitzpatrick Wrinkle Scale (MFWS). Separately, D-gal-induced senescence in HDFs was assessed via viability, SA-β-gal activity, senescence markers, ROS, antioxidant enzymes, SASP/ECM gene expression, and MAPK activation. GPR30 involvement was examined using antagonist G15, shRNA knockdown, and molecular docking. RESULTS: Topical TXA produced significantly greater MFWS reductions versus moisturizer alone at weeks 4, 8, and 12, with benefit persisting post-treatment. In HDFs, TXA preserved viability, reduced SA-β-gal positivity, attenuated p21/p16, restored Lamin B1, decreased ROS, and rescued antioxidant activities. TXA downregulated IL-6, IL-8, MMP1, and MMP3, and suppressed D-gal-induced ERK, JNK, and p38 phosphorylation. These effects were weakened by G15 or GPR30 knockdown; docking supported a stable TXA-GPR30 interaction. CONCLUSIONS: TXA showed clinical anti-wrinkle activity in melasma patients and protected HDFs from D-gal-induced senescence, partly via GPR30-dependent modulation of oxidative stress, SASP/ECM expression, and MAPK signalling. TXA is a promising candidate for skin ageing intervention.

Humans↗
PubMed2024

Remodeling of cytoskeleton, chromatin, and gene expression during mechanical rejuvenation of aged human dermal fibroblasts.

Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been explored. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. Here, we studied the cytoskeletal, genome-wide chromatin and transcriptional changes in young, aged, and mechanically rejuvenated fibroblasts using immunofluorescence, RNA sequencing, and Hi-C experiments. The mechanically rejuvenated aged fibroblasts, that had partially reset their transcription to a younger cell state, showed a local reorganization of the interchromosomal contacts and lamina-associated domains. Interestingly, the observed chromatin reorganization correlated with the transcriptional changes. Immunofluorescence experiments in the rejuvenated state confirmed increased actomyosin contractility like younger fibroblasts. In addition, the rejuvenated contractile properties were maintained over multiple cell passages. Overall, our results give an overview of how changes in the cytoskeleton, chromatin, and gene activity are connected to aging and rejuvenation.

Humans↗
PubMed1978

Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides.

The chemotactice response of human dermal fibroblasts of type I, II, and III human collagens and collagen-derived peptides was quantitated by an in vitro assay. All three native human collagens and constituent alpha chains can serve as chemoattractants for fibroblasts in vitro. When type I, II, and III collagens were digested by bacterial collagenase, the resulting peptides were also chemotactic. In addition, synthetic di- and tripeptides containing hydroxyproline were also chemotactic for fibroblasts. Since collagen is degraded and remodeled at sites of tissue injury and inflammation, these findings suggest that collagen and collagen-degradation peptides might function as chemotactic stimuli for fibroblasts in vivo and attract these cells to effect repair of damaged tissue.

Cell Line↗
PubMed2027

Generation of Transgene-Free Naive Human Induced Pluripotent Stem Cells from Somatic Cells Using a Modified Temperature-Sensitive Sendai Virus System.

The Sendai virus (SeV) vector system offers an efficient, nonintegrating approach to reprogram somatic cells into either naive or primed human induced pluripotent stem cells (iPSCs). Here, we describe a protocol to generate transgene-free naive iPSCs from human dermal fibroblasts (HDFs) and peripheral blood mononuclear cells (PBMCs) using a modified, temperature-sensitive SeV system. The method leverages LMYC in place of cMYC and an optional H1FOO-DD factor to enhance efficiency and uniformity, and employs a controlled temperature shift to facilitate vector clearance.

Humans↗
PubMed1979

Generation of a fibroblast chemotactic factor in serum by activation of complement.

When serum complement is activated by either the classical or alternative pathways, a factor with an apparent 80,000 mol wt is generated that is chemotactic for human dermal fibroblasts. The origin of this serum-derived chemotactic factor (SDCF) is not known; however, it may be a cleavage product from C5 because it is inactivated by monospecific antiserum to human C5, and it is not generated when the complement system is activated in human serum deficient in C5. SDCF is not chemotactic for human neutrophils or monocytes. Because SDCF is generated when serum complement is activated, it may function in vivo to attract connective tissue fibroblasts to sites of inflammatory reactions in which the complement system participates.

Cells, Cultured↗
PubMed2026

Cystathionine γ-Lyase-Dependent S-Sulfhydration of Smad3: A Novel Target to Alleviate Fibrosis in Systemic Sclerosis.

OBJECTIVE: The cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) axis has emerged as a key regulator in tissue fibrogenesis. This study aimed to explore the role of the CSE/H2S axis in systemic sclerosis (SSc) and to investigate its underlying mechanisms to identify promising therapeutic targets. METHODS: CSE/H2S levels were assessed in serum samples from 25 patients with SSc and 28 healthy controls. Human dermal fibroblasts from patients with SSc and healthy controls were used for functional studies, including propargylglycine (CSE inhibitor) treatment, Gyy4137, a slow-releasing hydrogen sulfide donor, CSE silencing, and CSE overexpression, combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based S-sulfhydration proteomics. Molecular dynamics simulations were performed to study the effects of S-sulfhydration on protein structure, and an Smad3 C121S (cysteine [Cys] 121 mutated to Ser) mutant was generated to verify the function targets of S-sulfhydration. In vivo, bleomycin-induced mouse models of skin and lung fibrosis were constructed to evaluate the effects of CSE overexpression. RESULTS: In human samples, CSE/H2S levels were reduced in SSc. CSE inhibition promoted extracellular matrix deposition. S-sulfhydration proteomics showed that S-sulfhydration levels were globally reduced in SSc compared to controls. CSE overexpression increased S-sulfhydration on Smad3, suppressed transforming growth factor β 1 (TGFβ1)/Smad3 signaling, mitigating skin fibrosis. Notably, Cys121 on Smad3, identified as a pivotal target for S-sulfhydration by proteomics, was shown to fine-tune its MH1 domain, with its mutation impairing the antifibrotic effects. In mice, CSE overexpression attenuated bleomycin-induced skin and lung fibrosis. CONCLUSION: Smad3 S-sulfhydration mediates the antifibrotic effect of CSE in SSc, highlighting it as a critical mechanism and promising therapeutic target.

Humans↗
PubMed2026

UVB photoprotection by thiourea and (thio)semicarbazone derivatives: cellular and molecular evidence.

BACKGROUND: Ultraviolet B (UVB) radiation is a major environmental stressor that contributes to oxidative stress, inflammation, DNA damage, and ultimately an increased risk of skin carcinogenesis. The development of safer, multifaceted UV filters with improved photostability and bioprotective properties remains an important research priority. Here, alkyl chain-conjugated thiourea (I-XIX) and aryl-linked (thio)semicarbazone (XX-XXV) derivatives have been systematically assessed for their photoprotective potential against UVB-induced cellular damage. METHODS: The UV absorption properties, molar absorptivity, and photostability of the test compounds were assessed through spectroscopic studies. Cytotoxicity, effective concentrations, and bioprotective effects of the compounds were evaluated using in vitro cellular methods. RESULTS: Several compounds exhibited robust UVB absorption with high molar absorptivity, particularly semicarbazone derivatives, while displaying minimal cytotoxicity to normal human dermal fibroblasts. Among the evaluated compounds, ten compounds were found to be more photostable than benzophenone (reference compound). Selected compounds significantly reduced UVB-induced intracellular reactive oxygen species and nitric oxide production, signifying effective attenuation of oxidative and nitrosative stress. In addition, compounds IV, XXI, and XXIII alleviated UVB-induced inflammatory cascades by diminishing Interleukin-1 beta (IL-1β) and Tumor Necrosis Factor alpha (TNF-α) levels. Therefore, these compounds also protected fibroblast morphology. Moreover, the same compounds protected from DNA damage by preventing UVB-induced genomic DNA fragmentation and formation of cyclobutane pyrimidine dimers. In particular, compound XXIII displayed selective UVB absorption, better photostability, low cytotoxicity, and moderate biological photoprotection (SPF 16). CONCLUSION: Together, the results suggest that thiourea and (thio)semicarbazone derivatives, notably compound XXIII, represent promising photoprotective scaffolds requiring further formulation, in vivo, permeability, phototoxicity, and safety studies to validate their potential as UV-filtering agents.

Humans↗
PubMed2026

Molecular-networking-based characterization of cytotoxic metabolites produced by the cyanobacterium Nostoc edaphicum CCNP1411.

Cyanobacteria of the genus Nostoc, known for their large genomes and rich repertoire of biosynthetic gene clusters, represent a prolific source of structurally diverse secondary metabolites with diverse biological activities, including cytotoxic effects. However, the identification of bioactive compounds is often hindered by low metabolite abundance and difficulties in isolating sufficient quantities for individual testing. In this study, we investigated the cytotoxic potential of chromatographic fractions obtained from Nostoc edaphicum CCNP1411 using a combination of bioassay-guided fractionation and LC-MS/MS-based feature-based molecular networking (FBMN). Cytotoxic activity was evaluated using the MTT assay across a panel of epithelial and neuronal cancer cell lines, as well as normal human dermal fibroblasts. The most active fractions, eluted with 80-90% MeOH, exhibited broad cytotoxic effects across all tested cancer cell lines. Molecular networking analysis revealed that these fractions were dominated by lipid derivatives, including lysophospholipids, monoacylglycerols, and free fatty acids, whereas previously described peptide metabolites were distributed across all fractions and were unlikely to be the main agents responsible for the observed activity. Targeted testing of selected commercially available lipid compounds confirmed their cytotoxic effects, with lysophospholipids showing the highest potency in selected cell lines. However, dose-response analysis indicated that most compounds exhibited limited potency at lower concentrations, as reflected by relatively high IC₅₀ values. Overall, our results demonstrate that lipid constituents, previously overlooked as bioactive metabolites produced by N. edaphicum CCNP1411, contribute significantly to the cytotoxic activity of the tested fractions. The application of molecular networking enabled the prioritization of bioactive metabolites and highlights its utility in linking chemical composition with biological effects in complex cyanobacterial extracts.

Bioactivity-guided fractionation↗
PubMed1977

A humoral cytotoxic substance produced by a human killer cell line.

The production of a cytotoxic factor synthesized by human haemic killer cells growing in vitro is described. The factor can be found extra- and intra-cellularly. It is released from the cells by an apocrine form of secretion, illustrated by light and electron micrographs. The culture fluid from 14C-labelled killer cells reveals numerous radioactive bands following SDS-gel electrophoresis. The killing factor is precipitated by 30 to 60% saturation of ammonium sulphate. Cultures of human rhabdomyosarcoma and osteosarcoma cells are more susceptible to the killer cells than normal human dermal or lung fibroblasts. During contact or killer with target cells a higher level of cytotoxic activity can be detected in the culture fluid. The cell-killing activity is completely inactivated by 30 min at 60 degrees C, but it is not absorbed by target cells during 1 h of incubation. The cytotoxic factor is unlikely to be an interferon since it did not prevent the replication of a wide range of viruses and only a low level of interferon could be detected in the culture medium. The introduction of Strep. faecalis into cultures of killer cells caused their transformation into immunoblast-like cells, indicating their lymphoid origin. The cells did not phagocytose the microorganism. When the humoral factor was injected into fibro-sarcoma-bearing mice approximately 50% survived, whereas all control animals died.

Animals↗
PubMed1979

Repair of ultraviolet light damage to the DNA of cultured human epidermal keratinocytes and fibroblasts.

Pure cultures of dermal fibroblasts and epidermal keratinocytes have been obtained from a single biopsy of newborn foreskin. The cells were labeled, exposed to several doses of UV light, and allowed to repair in the dark for 16 hr. The number of pyrimidine dimers before and after repair was assessed by measuring the numbers of sites in the DNA sensitive to a specific UV endonuclease. At all doses used, the extent of repair was similar in the cultured keratinocytes and cultured fibroblasts.

Cells, Cultured↗
PubMed1977

The lack of specificity of the sheep erythrocyte-T lymphocyte rosetting phenomenon.

One subpopulation of lymphocytes, thymus-derived (T) cells, is identified by its characteristic ability to form spontaneous rosettes with sheep erythrocytes (SRBC). However, the mechanism by which the rosettes form remains unknown. To gain more insight into the specificity of this phenomenon, the ability of SRBC to rosette with cells other thah lymphocytes was studied. All of the cell types utilized in this study (L cells, monkey liver cells, HeLa cells, and human liver, bladder, lung, parathyroid, and dermal fibroblasts), except neoplastic B lymphocytes, rosetted with SRBC. Viability was not a factor in the rosette formation. These findings suggest that the process of T lymphocyte-SRBC rosette formation is not due to a T cell-specific membrane receptor or antigen but may be due to a widely distributed basic substructure of the cell membrane.

Animals↗
PubMed1979

Chronic renal failure and atherogenesis--Serum factors stimulate the proliferation of human arterial smooth muscle cells.

To assess the role of serum factors in the genesis of accelerated vascular disease in chronic renal failure, human arterial smooth muscle cells (SMC) and dermal fibroblasts were grown in culture and the effects of serum from chronic dialysis patients on cell proliferation was studied. Exposure to serum from these renal failure patients was associated with significantly greater growth of both SMC and fibroblasts than that observed with control serum. A portion of this mitogenic effect appears to be related to the presence of a factor(s) which is heat stable, dialysable, and is contained in the lipoprotein deficient fraction of plasma of density greater than 1.25 g/dl. These findings suggest that circulating substances which stimulate the proliferation of SMC may contribute to accelerated cardiovascular disease in patients undergoing chronic dialysis treatment.

Arteries↗
PubMed1976

Effects of steriod hormones on human fibroblasts in vitro. II. Antagonism by androgens of cortisol-induced inhibition.

Inhibition of dermal activity by cortisol in culture was partially reversed by two naturally occurring androgens, testosterone and dihydrotestosterone. ACTH and the androgen precursor dehydroepiandrosterone sulphate showed not such antagonistic effect. These results suggest that increased production of adrenal androgens during ACTH therapy may account for the relative absnece of 'skin-thinning' and 'steroid-bruising' which are common side-effects of corticosteroid therapy.

Adrenocorticotropic Hormone↗
PubMed1979

Differentiation in human amniotic fluid cell cultures: chorionic gonadotropin production.

Two of the distinguishable cell classes subcultured from human amniotic fluid were examined for their capability to produce human chorionic gonadotropin (hCG) as determined by radioimmunoassay. The class that predominates in most cultures used for prenatal genetic diagnosis, previously termed AF (for amniotic fluid), secretes hCG into the culture medium. Dermal fibroblasts do not, nor does another type of cultured cell from amniotic fluid, previously termed F because of a resemblance to fibroblasts. Primary AF cultures produce more hCG than do subcultures. Evidence that this hormone is intact hCG is provided by its immunoreactivity with antisera raised against the beta-subunit and against the intact molecule of hCG. Furthermore, a dose-response curve for hormone in culture medium is parallel to that of highly purified intact hCG. It is postulated that AF cultures are derived from fetal membranes and retain properties of trophoblast.

Amniotic Fluid↗
PubMed1978

Development and differentiation of dermal cells in man.

Development and differentiation of the single free cells of mesenchyme and dermis of human embryos and fetuses from week 6 to term is described. From week 6 to week 14, three cell types are present: stellate general mesenchymal cells with long processes, phagocytic macrophages of probable yolk-sac origin, and a granule-secretory type of cell, which could be either a melanoblast or a mast stem cell. From week 14 to week 21, fibroblasts are numerous and active, and perineurial cells, pericytes, melanoblasts, mast cells, and Merkel cells can be individually identified. There is also present another cell type, possible of bone marrow origin, that may be ancestral to the Langerhans cell and that may be carried over into postanal dermis as the "histiocyte" or fixed dermal macrophage. From week 24 to term there is little change apart from the development of fat cells in the deeper dermis. Neither lymphocyte nor plasma cell was observed at any stage of development. These observations were used in the specification and identification of cells of fully developed postnatal dermis.

Cell Differentiation↗
PubMed2026

Generation of an induced pluripotent stem cell line, LGMi002-A, from a Bardet-Biedl Syndrome patient with a BBS5 homozygous pathogenic variant.

The human induced pluripotent stem cell (iPSC) line, iPSC-BBS5stbg1, derived from a patient with a Bardet-Biedl Syndrome (BBS) phenotype and carrying a BBS5 homozygous pathogenic variant: c.123delA, p.Gly42Glufs*11 is described. The reprogramming of the patient's dermal fibroblasts was achieved using the non-integrative Sendai virus system delivering the OCT4, SOX2, KLF4 and c-MYC (OSKM) transcription factors. The established iPSC line iPSC-BBS5stbg1 displays typical iPSC morphology, maintains genomic stability, and demonstrates the ability to differentiate into cell types representative of the three embryonic germ layers. This iPSC line constitutes robust and relevant cellular model for studying BBS-associated disease mechanisms and ciliary dysfunction.

Humans↗
PubMed1978

Enzymatic liberation of viable cells of human skin.

To obtain viable cells from normal human skin, clostridial collagenase was used. Crude collagenase digestion of collagen fibres and basal lamina results in free dermal cells and sheets of epidermis. The collagenase was tested at various concentrations, solvents and incubation periods. The specimens digested were either split or full thickness skin of varying size. The optimal result was obtained by using small (3mm across) split skin pieces incubated in 2 mg/ml collagenase. The choice of solvent MEM, MEM supplemented with serum, and Tris buffer, was less important. 3 hours' incubation the epidermis was peeled off in sheets and finally dissociated by trypsin-EDTA. The corium was completely digested after 6 hours. After 6 hours' incubation no viable cells could be seen. The epidermal cells appeared mainly as polygonal cells of various sizes and a few little dendritic cells. The dermal cells had a heterogeneous morphology during the first weeks of cultivation. After 2 weeks the cells appeared as fibroblast-like cells.

Cell Separation↗