Cells

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Open AccessReview

Recent Advances in Elucidating the Genetic Mechanisms of Nephrogenesis Using Zebrafish

by Christina N. Cheng, Valerie A. Verdun and Rebecca A. Wingert

Cells 2015, 4(2), 218-233; https://doi.org/10.3390/cells4020218 - 27 May 2015

Cited by 16 | Viewed by 6896

The kidney is comprised of working units known as nephrons, which are epithelial tubules that contain a series of specialized cell types organized into a precise pattern of functionally distinct segment domains. There is a limited understanding of the genetic mechanisms that establish [...] Read more.

The kidney is comprised of working units known as nephrons, which are epithelial tubules that contain a series of specialized cell types organized into a precise pattern of functionally distinct segment domains. There is a limited understanding of the genetic mechanisms that establish these discrete nephron cell types during renal development. The zebrafish embryonic kidney serves as a simplified yet conserved vertebrate model to delineate how nephron segments are patterned from renal progenitors. Here, we provide a concise review of recent advances in this emerging field, and discuss how continued research using zebrafish genetics can be applied to gain insights about nephrogenesis. Full article

(This article belongs to the Special Issue The Kidney: Development, Disease and Regeneration)

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Open AccessReview

WIPI-Mediated Autophagy and Longevity

by Mona Grimmel, Charlotte Backhaus and Tassula Proikas-Cezanne

Cells 2015, 4(2), 202-217; https://doi.org/10.3390/cells4020202 - 22 May 2015

Cited by 39 | Viewed by 11467

Abstract

Autophagy is a lysosomal degradation process for cytoplasmic components, including organelles, membranes, and proteins, and critically secures eukaryotic cellular homeostasis and survival. Moreover, autophagy-related (ATG) genes are considered essential for longevity control in model organisms. Central to the regulatory relationship between autophagy and [...] Read more.

Autophagy is a lysosomal degradation process for cytoplasmic components, including organelles, membranes, and proteins, and critically secures eukaryotic cellular homeostasis and survival. Moreover, autophagy-related (ATG) genes are considered essential for longevity control in model organisms. Central to the regulatory relationship between autophagy and longevity is the control of insulin/insulin-like growth factor receptor-driven activation of mTOR (mechanistic target of rapamycin), which inhibits WIPI (WD repeat protein interacting with phosphoinositides)-mediated autophagosome formation. Release of the inhibitory mTOR action on autophagy permits the production of PI3P (phosphatidylinositol-3 phosphate), predominantly at the endoplasmic reticulum, to function as an initiation signal for the formation of autophagosomes. WIPI proteins detect this pool of newly produced PI3P and function as essential PI3P effector proteins that recruit downstream autophagy-related (ATG) proteins. The important role of WIPI proteins in autophagy is highlighted by functional knockout of the WIPI homologues ATG-18 and EPG-6 in Caenorhabditis elegans (C. elegans). Adult lifespan is significantly reduced in ATG-18 mutant animals, demonstrating that longevity as such is crucially determined by essential autophagy factors. In this review we summarize the role of WIPI proteins and their C. elegans homologues with regard to the molecular basis of aging. As the development of strategies on how to increase health span in humans is increasingly appreciated, we speculate that targeting WIPI protein function might represent a therapeutic opportunity to fight and delay the onset of age-related human diseases. Full article

(This article belongs to the Special Issue Autophagy)

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Open AccessReview

Scavenger Receptor Structure and Function in Health and Disease

by Izma Abdul Zani, Sam L. Stephen, Nadeem A. Mughal, David Russell, Shervanthi Homer-Vanniasinkam, Stephen B. Wheatcroft and Sreenivasan Ponnambalam

Cells 2015, 4(2), 178-201; https://doi.org/10.3390/cells4020178 - 22 May 2015

Cited by 251 | Viewed by 23077

Abstract

Scavenger receptors (SRs) are a ‘superfamily’ of membrane-bound receptors that were initially thought to bind and internalize modified low-density lipoprotein (LDL), though it is currently known to bind to a variety of ligands including endogenous proteins and pathogens. New family of SRs and [...] Read more.

Scavenger receptors (SRs) are a ‘superfamily’ of membrane-bound receptors that were initially thought to bind and internalize modified low-density lipoprotein (LDL), though it is currently known to bind to a variety of ligands including endogenous proteins and pathogens. New family of SRs and their properties have been identified in recent years, and have now been classified into 10 eukaryote families, defined as Classes A-J. These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence. Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens. SR members regulate pathophysiological states including atherosclerosis, pathogen infections, immune surveillance, and cancer. Here, we review our current understanding of SR structure and function implicated in health and disease. Full article

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Open AccessReview

What is Known Regarding the Participation of Factor Nrf-2 in Liver Regeneration?

by José A. Morales-González, Eduardo Madrigal-Santillán, Ángel Morales-González, Mirandeli Bautista, Evila Gayosso-Islas and Cecilia Sánchez-Moreno

Cells 2015, 4(2), 169-177; https://doi.org/10.3390/cells4020169 - 20 May 2015

Cited by 25 | Viewed by 6276

Abstract

It has been known for years that, after chemical damage or surgical removal of its tissue, the liver initiates a series of changes that, taken together, are known as regeneration, which are focused on the recovery of lost or affected tissue in terms [...] Read more.

It has been known for years that, after chemical damage or surgical removal of its tissue, the liver initiates a series of changes that, taken together, are known as regeneration, which are focused on the recovery of lost or affected tissue in terms of the anatomical or functional aspect. The Nuclear factor-erythroid 2-related factor (Nrf-2) is a reduction-oxidation reaction (redox)-sensitive transcriptional factor, with the basic leucine Zipper domain (bZIP) motif, encoding the NFE2L2 gene. The Keap1-Nrf2-ARE pathway is transcendental in the regulation of various cellular processes, such as antioxidant defenses, redox equilibrium, the inflammatory process, the apoptotic processes, intermediate metabolism, detoxification, and cellular proliferation. Some reports have demonstrated the regulator role of Nrf-2 in the cellular cycle of the hepatocyte, as well as in the modulation of the antioxidant response and of apoptotic processes during liver regeneration. It has been reported that there is a delay in liver regeneration after Partial hepatectomy (PH) in the absence of Nrf-2, and similarly as a regulator of hepatic cytoprotection due to diverse chemical or biological agents, and in diseases such as hepatitis, fibrosis, cirrhosis, and liver cancer. This regulator/protector capacity is due to the modulation of the Antioxidant response elements (ARE). It is postulated that oxidative stress (OS) can participate in the initial stages of liver regeneration and that Nrf-2 can probably participate. Studies are lacking on the different initiation stages, maintenance, and the termination of liver regeneration alone or with ethanol. Full article

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Open AccessReview

HDAC Family Members Intertwined in the Regulation of Autophagy: A Druggable Vulnerability in Aggressive Tumor Entities

by Emily Koeneke, Olaf Witt and Ina Oehme

Cells 2015, 4(2), 135-168; https://doi.org/10.3390/cells4020135 - 23 Apr 2015

Cited by 71 | Viewed by 10431

Abstract

The exploitation of autophagy by some cancer entities to support survival and dodge death has been well-described. Though its role as a constitutive process is important in normal, healthy cells, in the milieu of malignantly transformed and highly proliferative cells, autophagy is critical [...] Read more.

The exploitation of autophagy by some cancer entities to support survival and dodge death has been well-described. Though its role as a constitutive process is important in normal, healthy cells, in the milieu of malignantly transformed and highly proliferative cells, autophagy is critical for escaping metabolic and genetic stressors. In recent years, the importance of histone deacetylases (HDACs) in cancer biology has been heavily investigated, and the enzyme family has been shown to play a role in autophagy, too. HDAC inhibitors (HDACi) are being integrated into cancer therapy and clinical trials are ongoing. The effect of HDACi on autophagy and, conversely, the effect of autophagy on HDACi efficacy are currently under investigation. With the development of HDACi that are able to selectively target individual HDAC isozymes, there is great potential for specific therapy that has more well-defined effects on cancer biology and also minimizes toxicity. Here, the role of autophagy in the context of cancer and the interplay of this process with HDACs will be summarized. Identification of key HDAC isozymes involved in autophagy and the ability to target specific isozymes yields the potential to cripple and ultimately eliminate malignant cells depending on autophagy as a survival mechanism. Full article

(This article belongs to the Special Issue Autophagy)

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Open AccessCorrection

Correction: Santos, R.S., et al. Improvement of IFNγ ELISPOT Performance Following Overnight Resting of Frozen PBMC Samples Confirmed Through Rigorous Statistical Analysis. Cells 2015, 4, 1-18

by Radleigh Santos, Alcinette Buying, Nazila Sabri, John Yu, Anthony Gringeri, James Bender, Sylvia Janetzki, Clemencia Pinilla and Valeria A. Judkowski

Cells 2015, 4(2), 133-134; https://doi.org/10.3390/cells4020133 - 21 Apr 2015

Cited by 1 | Viewed by 5002

Abstract

The authors wish to make the following corrections to this paper [1]: [...] Full article

(This article belongs to the Special Issue ELISPOT Research)

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Open AccessReview

Signaling during Kidney Development

by Mirja Krause, Aleksandra Rak-Raszewska, Ilkka Pietilä, Susan E. Quaggin and Seppo Vainio

Cells 2015, 4(2), 112-132; https://doi.org/10.3390/cells4020112 - 10 Apr 2015

Cited by 49 | Viewed by 13169

Abstract

The kidney plays an essential role during excretion of metabolic waste products, maintenance of key homeostasis components such as ion concentrations and hormone levels. It influences the blood pressure, composition and volume. The kidney tubule system is composed of two distinct cell populations: [...] Read more.

The kidney plays an essential role during excretion of metabolic waste products, maintenance of key homeostasis components such as ion concentrations and hormone levels. It influences the blood pressure, composition and volume. The kidney tubule system is composed of two distinct cell populations: the nephrons forming the filtering units and the collecting duct system derived from the ureteric bud. Nephrons are composed of glomeruli that filter the blood to the Bowman’s capsule and tubular structures that reabsorb and concentrate primary urine. The collecting duct is a Wolffian duct-derived epithelial tube that concentrates and collects urine and transfers it via the renal pelvis into the bladder. The mammalian kidney function depends on the coordinated development of specific cell types within a precise architectural framework. Due to the availability of modern analysis techniques, the kidney has become a model organ defining the paradigm to study organogenesis. As kidney diseases are a problem worldwide, the understanding of mammalian kidney cells is of crucial importance to develop diagnostic tools and novel therapies. This review focuses on how the pattern of renal development is generated, how the inductive signals are regulated and what are their effects on proliferation, differentiation and morphogenesis. Full article

(This article belongs to the Special Issue The Kidney: Development, Disease and Regeneration)

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Cells, Volume 4, Issue 2 (June 2015) – 7 articles , Pages 112-233

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