Search

Mucin 1 (or MUC1) is a heterodimeric transmembrane glycoprotein expressed on the apical surface of polarized epithelial cells in several tissues including the kidney. Recent studies have revealed several novel roles for MUC1 in the kidney, potentially including bacterial infection, mineral balance, and genetic interstitial kidney disease, even though MUC1 levels are reduced not only in the kidney but in all tissues due to MUC1 mutations. A careful localization of MUC1 in discrete segments of the nephron is a first step in understanding the multiple functional roles of MUC1 in the kidney. Most published reports of MUC1 expression to date have been largely confined to cultured cells, tumor tissues, selective nephron segments of experimental rodents, and very few studies have been performed using human kidney tissues. Given the rising attention to the role of MUC1 in differing components of renal physiology, we carefully examined the kidney distribution of MUC1 in both human and mouse kidney sections using well-defined markers for different nephron segments or cell types. We further extended our investigation to include sections of early stages of mouse kidney development and upon injury in humans. We included staining for MUC1 in urothelial cells, the highly specialized epithelial cells lining the renal pelvis and bladder. These data implicate a role for MUC1 in antimicrobial defense. Our study provides the groundwork to test the physiological relevance of MUC1 in the urinary tract.

Acute kidney injury (AKI) is a frequent complication of sepsis that increases mortality and the risk of progression to chronic kidney disease. However, the mechanisms leading to sepsis-associated AKI are still poorly understood. The recognition that sepsis induces organ dysfunction in the absence of overt necrosis or apoptosis has led to the consideration that tubular epithelial cells (TEC) may deploy defense mechanisms to survive the insult. This concept dovetails well with the notion that the defense against infection does not only depend on the capacity of the immune system to limit the microbial load (known as resistance), but also on the capacity of cells and tissues to limit tissue injury (known as tolerance). In this review, we discuss the importance of TEC metabolic reprogramming as a defense strategy during sepsis, and how this cellular response is likely to operate through a tolerance mechanism. We discuss the fundamental role of specific regulatory nodes and of mitochondria in orchestrating this response, and how this opens avenues for the exploration of targeted therapeutic strategies to prevent or treat sepsis-associated AKI.

Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of the critically ill patient and is associated with unacceptable morbidity and mortality. Prevention of S-AKI is difficult because by the time patients seek medical attention, most have already developed acute kidney injury. Thus, early recognition is crucial to provide supportive treatment and limit further insults. Current diagnostic criteria for acute kidney injury has limited early detection; however, novel biomarkers of kidney stress and damage have been recently validated for risk prediction and early diagnosis of acute kidney injury in the setting of sepsis. Recent evidence shows that microvascular dysfunction, inflammation, and metabolic reprogramming are 3 fundamental mechanisms that may play a role in the development of S-AKI. However, more mechanistic studies are needed to better understand the convoluted pathophysiology of S-AKI and to translate these findings into potential treatment strategies and add to the promising pharmacologic approaches being developed and tested in clinical trials., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)