Catizone Angela, Ricci Giulia, Caruso Maria, Galdieri Michela, Scheri Katia Corano, Di Paolo Virginia, Canipari Rita
Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Section of Histology and Embryology, Sapienza University of Rome, Via A. Scarpa 16, 00161 Rome, Italy.
Department of Experimental Medicine, Histology and Embryology Laboratory, School of Medicine, Second University of Naples, Via Luciano Armanni 5, 80138 Naples, Italy.
Biomedicines. 2015 Jan 28;3(1):89-109. doi: 10.3390/biomedicines3010089.
The presence of the HGF/Met system in the testicular myoid cells was first discovered by our group. However, the physiological role of this pathway remains poorly understood. We previously reported that HGF increases uPA secretion and TGF-β activation in cultured tubular fragments and that HGF is maximally expressed at Stages VII-VIII of the seminiferous epithelium cycle, when myoid cell contraction occurs. It is well known that the HGF/Met pathway is involved in cytoskeletal remodeling; moreover, the interaction of uPA with its receptor, uPAR, as well as the activation of TGF-β have been reported to be related to the actin cytoskeleton contractility of smooth muscle cells. Herein, we report that HGF induces actin cytoskeleton remodeling in isolated myoid cells and myoid cell contraction in cultured seminiferous tubules. To better understand these phenomena, we evaluated: (1) the regulation of the uPA machinery in isolated myoid cells after HGF administration; and (2) the effect of uPA or Met inhibition on HGF-treated tubular fragments. Because uPA activates latent TGF-β, the secretion of this factor was also evaluated. We found that both uPA and TGF-β activation increase after HGF administration. In testicular tubular fragments, HGF-induced TGF-β activation and myoid cell contraction are abrogated by uPA or Met inhibitor administration.
我们团队首次发现睾丸肌样细胞中存在HGF/Met系统。然而，该信号通路的生理作用仍知之甚少。我们之前报道过，HGF可增加培养的肾小管片段中尿激酶型纤溶酶原激活物（uPA）的分泌及转化生长因子-β（TGF-β）的激活，并且HGF在生精上皮周期的VII-VIII期表达最高，此时肌样细胞会发生收缩。众所周知，HGF/Met信号通路参与细胞骨架重塑；此外，据报道uPA与其受体uPAR的相互作用以及TGF-β的激活与平滑肌细胞的肌动蛋白细胞骨架收缩性有关。在此，我们报道HGF可诱导分离的肌样细胞发生肌动蛋白细胞骨架重塑，并使培养的生精小管中的肌样细胞收缩。为了更好地理解这些现象，我们评估了：（1）给予HGF后分离的肌样细胞中uPA机制的调节；（2）uPA或Met抑制对HGF处理的肾小管片段的影响。由于uPA可激活潜伏的TGF-β，因此也评估了该因子的分泌情况。我们发现给予HGF后uPA和TGF-β的激活均增加。在睾丸肾小管片段中，给予uPA或Met抑制剂可消除HGF诱导的TGF-β激活和肌样细胞收缩。
