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1.
Artigo em Inglês | WPRIM | ID: wpr-971484

RESUMO

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.


Assuntos
Humanos , Células Estreladas do Fígado/patologia , Receptores de Calcitriol , Cirrose Hepática/patologia , Macrófagos/metabolismo
2.
Military Medical Sciences ; (12): 224-227, 2014.
Artigo em Chinês | WPRIM | ID: wpr-448118

RESUMO

Understanding heart development at a molecular level is a prerequisite for uncovering the causes of congenital heart diseases .Such knowledge can also greatly benefit therapeutic approaches that try to enhance cardiac regeneration or that involve the differentiation of resident cardiac progenitor cells .Wnt proteins have been shown to play multiple roles dur-ing cardiac development .They are extracellular growth factors that activate different intracellular signaling branches .Here, we summarize our current understanding of how these factors affect different aspects of cardiogenesis , from early specifica-tion of cardiac progenitors to later developmental steps , such as remodeling processes .

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