Expression of hypoxia-inducible factor (HIF)-1a-vascular endothelial growth factor (VEGF)-inhibitory growth factor (ING)-4- axis in sarcoidosis patients

缺氧诱导因子(HIF)-1a-血管内皮生长因子(VEGF)-抑制生长因子(ING)-4轴在结节病患者中的表达

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作者:Argyris Tzouvelekis, Paschalis Ntolios, Andreas Karameris, Anastasios Koutsopoulos, Panagiotis Boglou, Andreas Koulelidis, Kostas Archontogeorgis, George Zacharis, Fotis Drakopanagiotakis, Paschalis Steiropoulos, Stavros Anevlavis, Vlassis Polychronopoulos, Dimitrios Mikroulis, Demosthenes Bouros

Background

Sarcoidosis is a granulomatous disorder of unknown etiology. The term of immunoangiostasis has been addressed by various studies as potentially involved in the disease pathogenesis. The

Conclusions

Our data suggest an impairment of the HIF-1a - VEGF axis, potentialy arising by ING4 overexpression and ultimately resulting in angiostasis and monocyte recruitment within granulomas. The concept of immunoangiostasis as a possible protection mechanism against antigens of infectious origin needs further research to be verified.

Methods

A total of 37 patients with sarcoidosis stages II-III were recruited in our study. Tissue microarray technology coupled with immunohistochemistry analysis were applied to video-assisted thoracoscopic surgery (VATS) lung biopsy samples collected from 37 sarcoidosis patients and 24 controls underwent surgery for benign lesions of the lung. Computerized image analysis was used to quantify immunohistochemistry

Results

HIF-1a and VEGF-ING4 expression, both in protein and mRNA level, was found to be downregulated and upregulated, respectively, in sarcoidosis samples compared to controls. Immunohistochemistry coupled with computerized image analysis revealed minimal expression of HIF-1a within sarcoid granulomas whereas an abundant staining of ING4 and VEGF in epithelioid cells was also visualized. Conclusions: Our data suggest an impairment of the HIF-1a - VEGF axis, potentialy arising by ING4 overexpression and ultimately resulting in angiostasis and monocyte recruitment within granulomas. The concept of immunoangiostasis as a possible protection mechanism against antigens of infectious origin needs further research to be verified.

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