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Matrix metalloproteinase-10 (MMP-10) is a zinc-dependent endopeptidase involved in regulating a wide range of biologic processes, such as apoptosis, cell proliferation, and tissue remodeling. However, the role of MMP-10 in the pathogenesis of acute kidney injury (AKI) is unknown. In this study, we show that MMP-10 was upregulated in the kidneys and predominantly localized in the tubular epithelium in various models of AKI induced by ischemia/reperfusion (IR) or cisplatin. Overexpression of exogenous MMP-10 ameliorated AKI, manifested by decreased serum creatinine, blood urea nitrogen, tubular injury and apoptosis, and increased tubular regeneration. Conversely, knockdown of endogenous MMP-10 expression aggravated kidney injury. Interestingly, alleviation of AKI by MMP-10 in vivo was associated with the activation of epidermal growth factor receptor (EGFR) and its downstream AKT and extracellular signal-regulated kinase-1 and 2 (ERK1/2) signaling. Blockade of EGFR signaling by erlotinib abolished the MMP-10-mediated renal protection after AKI. In vitro, MMP-10 potentiated EGFR activation and protected kidney tubular cells against apoptosis induced by hypoxia/reoxygenation or cisplatin. MMP-10 was colocalized with heparin-binding EGF-like growth factor (HB-EGF) in vivo and activated it by a process of proteolytical cleavage in vitro. These studies identify HB-EGF as a previously unrecognized substrate of MMP-10. Our findings also underscore that MMP-10 can protect against AKI by augmenting EGFR signaling, leading to promotion of tubular cell survival and proliferation after injury.

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Matrix metalloproteinase-10 (MMP-10) is a zinc-dependent endopeptidase with the ability to degrade a broad spectrum of extracellular matrices and other protein substrates. The expression of MMP-10 is induced in acute kidney injury (AKI) and chronic kidney disease (CKD), as well as in renal cell carcinoma (RCC). During the different stages of kidney injury, MMP-10 may exert distinct functions by cleaving various bioactive substrates including heparin-binding epidermal growth factor (HB-EGF), zonula occludens-1 (ZO-1), and pro-MMP-1, -7, -8, -9, -10, -13. Functionally, MMP-10 is reno-protective in AKI by promoting HB-EGF-mediated tubular repair and regeneration, whereas it aggravates podocyte dysfunction and proteinuria by disrupting glomerular filtration integrity via degrading ZO-1. MMP-10 is also involved in cancerous invasion and emerges as a promising therapeutic target in patients with RCC. As a secreted protein, MMP-10 could be detected in the circulation and presents an inverse correlation with renal function. Due to the structural similarities between MMP-10 and the other MMPs, development of specific inhibitors targeting MMP-10 is challenging. In this review, we summarize our current understanding of the role of MMP-10 in kidney diseases and discuss the potential mechanisms of its actions.

This article mainly elaborates the management games ---staff first, unifying to the investigation to Chinese Enterprise staff practical work condition, it explores the necessity and superiority of staff first. Continuously, this article argues that stuff regards the customer as God while the managers should place the staff first. This circle will cause the enterprise to be vital and vigor, it also fully displays the competitive power of enterprise, then the enterprise in intense develops competitively in long-term. Keywords: Staff first, Cultivate leaders, Self-management teamSeeking and satisfying the customer s' needs, setting the highest goal for customers, since this is the center which continuously has been revolved by the enterprise management and operation. However, in the world, all science's and technology's progress, material wealth's creation, social productive forces' development as well as the social economy system's movement cannot leave from private work, service and management. To establish and implement "the staff first" strategy, it not only controls person's management, but also serves for person's management, it pursues not only for turnover, but in strengthens to foundation of the staff loyalty to the enterprise, just to obtain the sustained development. Specially, it is especially important to Chinese Enterprise in the new times.

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