NF-κB and tPA Signaling in Kidney and Other Diseases.

Samantha White,Kebin Hu,Ling Lin

doi:10.3390/cells9061348

Abstract

The activation of the nuclear factor-κB (NF-κB) pathway plays a central role in the initiation and progression of inflammation, which contributes to the pathogenesis and progression of various human diseases including kidney, brain, and other diseases. Tissue plasminogen activator (tPA), a serine protease regulating homeostasis of blood coagulation, fibrinolysis, and matrix degradation, has been shown to act as a cytokine to trigger profound receptor-mediated intracellular events, modulate the NF-κB pathway, and mediate organ dysfunction and injury. In this review, we focus on the current understanding of NF-κB and tPA signaling in the development and progression of kidney disease. Their roles in the nervous and cardiovascular system are also briefly discussed.

Highlights

Chronic kidney disease (CKD) is one of the most common chronic diseases in the world
We further found that Tissue plasminogen activator (tPA)-induced matrix metalloproteinases (MMPs)-9 expression does not depend on its protease activity, but instead, through a signaling cascade with LRP-1 acting as a cell membrane receptor for tPA
We have found that tPA induces the the expression of the proinflammatory chemokines as interferon-γ-inducible protein expression of the proinflammatory chemokines such such as interferon-γ-inducible protein (IP)-10(IP)-10 and and macrophage inflammatory protein (MIP)-1 α in macrophages and promote the infiltration macrophage inflammatory protein (MIP)-1 α in macrophages and promote the infiltration ofof macrophages anan obstruction-induced

Summary

Introduction

Chronic kidney disease (CKD) is one of the most common chronic diseases in the world. The inflammation is further exasperated as these cells stimulate the production of more pro-inflammatory genes by activating transcription factors, of which nuclear factor-κB (NF-κB) is the most predominant and well-studied one. Increased NF-κB activity is predominant in many diseases, including CKD [6]. TPA has been shown to operate as a cytokine to regulate an array of intracellular signaling events [7]. Many studies have demonstrated that tPA expression, much like NF-κB, is increased with the initiation and progression of CKD [8]. TPA regulates inflammatory responses as a cytokine by modulating the NF-κB pathway. We will highlight the roles of tPA signaling and the NF-κB pathway in kidney and other diseases, such as cerebral ischemic stroke and cardiovascular diseases

Discovery and Structure

NF-κB Activation and Signaling Pathways

NF-κB as a Regulator of Inflammation

NF-κB and Renal Inflammation

Conclusions