RESUMEN
Keloids are benign fibroproliferative diseases with abnormally proliferated bulges beyond the edge of the skin lesions, and they are characterized by uncontrolled fibroblast proliferation and excessive extracellular matrix deposition in the dermis. However, the definite mechanisms that increase fibroblast proliferation and collagen deposition in keloids remain unclear. Thrombospondin 1 (TSP1) has been suggested to play an important role in wound healing and fibrotic disorders, but its role in keloids is unknown. In this study, we aimed to clarify the specific role of TSP1 in keloids and explore the potential mechanism. Our results demonstrated that TSP1 was highly expressed in keloid lesions compared to normal skin. Knockdown of TSP1 in keloid fibroblasts decreased cell proliferation and collagen I deposition. Exogenous TSP1 treatment increased cell proliferation and collagen I deposition in normal fibroblasts. We further investigated the underlying mechanism and found that TSP1 promoted fibroblast proliferation and extracellular matrix deposition by upregulating the IL6/JAK2/STAT3 pathway. Moreover, we verified that TSP1 expression was positively correlated with IL6/STAT3 signalling activity in keloids. Taken together, our findings indicate that TSP1 promotes keloid development via the IL6/JAK2/STAT3 signalling pathway and blocking TSP1 may represent a potential strategy for keloid therapy.
Asunto(s)
Queloide , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Proliferación Celular , Células Cultivadas , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Humanos , Interleucina-6/metabolismo , Janus Quinasa 2/metabolismo , Queloide/metabolismo , Factor de Transcripción STAT3/metabolismo , Trombospondina 1/metabolismoRESUMEN
OBJECTIVE: To evaluate the ability of two scoring systems (CHA2DS2-VASc score and CHA2DS2-VASc+hyperlipidaemia+smoking [CHA2DS2-VASc-HS score]) to predict in-stent restenosis (ISR) among patients undergoing drug-eluting stent (DES) implantation. METHODS: This retrospective study enrolled patients who underwent coronary angiography to assess coronary artery disease severity secondary to a diagnosis of stable angina or acute coronary syndrome that subsequently underwent DES implantations. Demographic, clinical, angiographic and biochemical parameters were compared between those patients that experienced ISR and those that did not during the study follow-up period. Univariate and multivariate logistic regression analyses were used to evaluate associations between the baseline parameters, the two scoring systems and ISR risk. RESULTS: A total of 358 patients (non-ISR group n = 316; ISR group n = 42) participated in the study. Compared with the non-ISR group, more patients in the ISR group had diabetes mellitus and received stents with smaller diameters but longer lengths. There were no significant differences with regard the predictive ability for ISR of either the CHA2DS2-Vasc or the CHA2DS2-Vasc-HS scores. Multivariate logistic regression analyses demonstrated that stent diameter, follow-up duration and glycosylated haemoglobin were independent risk factors for ISR. CONCLUSIONS: The CHA2DS2-Vasc and CHA2DS2-Vasc-HS scores did not predict ISR in patients after coronary DES placement.