Endogenous hydrogen sulphide deficiency and exogenous hydrogen sulphide supplement regulate skin fibroblasts proliferation via necroptosis.
Exp Dermatol
; 33(1): e14972, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-37975594
ABSTRACT
An excessive proliferation of skin fibroblasts usually results in different skin fibrotic diseases. Hydrogen sulphide (H2 S) is regarded as an important endogenous gasotransmitter with various functions. The study aimed to investigate the roles and mechanisms of H2 S on primary mice skin fibroblasts proliferation. Cell proliferation and collagen synthesis were assessed with the expression of α-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), Collagen I and Collagen III. The degree of oxidative stress was evaluated by dihydroethidium (DHE) and MitoSOX staining. Mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. Necroptosis was evaluated with TDT-mediated dUTP nick end labelling (TUNEL) and expression of receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL). The present study found that α-SMA, PCNA, Collagen I and Collagen III expression were increased, oxidative stress was promoted, ΔΨm was impaired and positive rate of TUNEL staining, RIPK1 and RIPK3 expression as well as MLKL phosphorylation were all enhanced in skin fibroblasts from cystathionine γ-lyase (CSE) knockout (KO) mice or transforming growth factor-ß1 (TGF-ß1, 10 ng/mL)-stimulated mice skin fibroblasts, which was restored by exogenous sodium hydrosulphide (NaHS, 50 µmol/L). In conclusion, endogenous H2 S production impairment in CSE-deficient mice accelerated skin fibroblasts proliferation via promoted necroptosis, which was attenuated by exogenous H2 S. Exogenous H2 S supplement alleviated proliferation of skin fibroblasts with TGF-ß1 stimulation via necroptosis inhibition. This study provides evidence for H2 S as a candidate agent to prevent and treat skin fibrotic diseases.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Sulfetos
/
Sulfeto de Hidrogênio
Limite:
Animals
Idioma:
En
Revista:
Exp Dermatol
Assunto da revista:
DERMATOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China