ijms-logo

Journal Browser

Journal Browser

Special Issue "Rho Family Proteins and Their Regulators in Kidney Physiology and Pathology"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 15 September 2021.

Special Issue Editors

Dr. Katalin Szászi
E-Mail Website
Guest Editor
Keenan Research Centre for Biomedical Science, Toronto, Canada
Interests: Tubular epithelial biology; Rho family small GTPases; tight junctions; inflammatory signalling; guanine nucleotide exchange factors; claudins; epithelial-mesenchymal transition
Dr. Andras Kapus
E-Mail Website
Guest Editor
Keenan Research Centre for Biomedical Science, Toronto, Canada
Interests: renal fibrosis; epithelium; profibrotic epithelial phenotype; transcription factors; Myocardin-related transcription factor; Yap/TAZ signaling; cytoskeleton; fibrogenic cytokines; primary cilium; polycystic kidney disease
Dr. Tomoko Takano
E-Mail Website
Guest Editor
Department of Medicine, Division of Nephrology, Faculty of Medicine, McGill University
Interests: nephrotic syndrome; proteinuria; podocytes; Rho-GTPases; cytoskeleton

Special Issue Information

Dear Colleagues,

Rho GTPase proteins form a subgroup of the Ras superfamily. In mammals, this group consists of 20 members that can be divided into subfamilies, including the best characterized Rac, Cdc42, and RhoA subfamilies as well as the lesser known groups of Rnd, RhoD/F, RhoH, RhoU/V, RhoBTB, and RhoT proteins. These proteins are at the center of an ever-increasing array of vital biological processes. The best studied members, RhoA, Rac1, and Cdc42, were initially characterized as central regulators of actin dynamics. Members of the Rho family subsequently emerged as vital orchestrators of diverse general cells functions, including gene transcription, vesicular trafficking, cell cycle progression, migration, polarity and differentiation control, as well as more specialized functions such as the control of enzymes generating reactive oxygen species. These diverse downstream effects are achieved through a multitude of effectors. In fact, Rho proteins and their regulators and effectors form complex, highly plastic, intertwined signaling networks. We have only started unraveling the details of how regulatory proteins finetune stimulus-specific Rho GTPase activation, selectively connecting a multitude of regulatory inputs to specific effectors. Detailed characterization of the spatiotemporal control and coordination of these networks will yield improved understanding of their physiological and pathological roles.

In recent years, our understanding of the vital roles of the Rho family in kidney biology has significantly increased, although our knowledge is mostly limited to the best characterized members of this large family. Accumulating evidence now implicates many Rho protein-dependent pathways in various kidney diseases, including glomerular diseases, kidney fibrosis, and developmental disorders. The aim of this Special Issue is to collect original contributions and review articles on all aspects of research on Rho family GTPases, as well as their regulators and effectors, in the broad context of kidney biology and pathology.

Suggested topics include but are not limited to research exploring the role and regulation of Rho proteins, regulators, and effectors in:

Podocyte biology

Tubular transport and its disorders

Glomerular diseases

Acute kidney injury

Inflammatory processes

Chronic kidney disease and fibrosis

Diabetic nephropathy

Polycystic kidney disease

Dr. Katalin Szászi
Dr. Andras Kapus
Dr. Tomoko Takano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Rho family small GTPases
  • Rho-related signalling in renal cells
  • Renal (patho)physiology
  • acute and chronic kidney disease
  • hereditary kidney diseases
  • glomerulopathy
  • diabetic nephropathy

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessCommunication
Activin A and Cell-Surface GRP78 Are Novel Targetable RhoA Activators for Diabetic Kidney Disease
Int. J. Mol. Sci. 2021, 22(6), 2839; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062839 - 11 Mar 2021
Viewed by 325
Abstract
Diabetic kidney disease (DKD) is the leading cause of kidney failure. RhoA/Rho-associated protein kinase (ROCK) signaling is a recognized mediator of its pathogenesis, largely through mediating the profibrotic response. While RhoA activation is not feasible due to the central role it plays in [...] Read more.
Diabetic kidney disease (DKD) is the leading cause of kidney failure. RhoA/Rho-associated protein kinase (ROCK) signaling is a recognized mediator of its pathogenesis, largely through mediating the profibrotic response. While RhoA activation is not feasible due to the central role it plays in normal physiology, ROCK inhibition has been found to be effective in attenuating DKD in preclinical models. However, this has not been evaluated in clinical studies as of yet. Alternate means of inhibiting RhoA/ROCK signaling involve the identification of disease-specific activators. This report presents evidence showing the activation of RhoA/ROCK signaling both in vitro in glomerular mesangial cells and in vivo in diabetic kidneys by two recently described novel pathogenic mediators of fibrosis in DKD, activins and cell-surface GRP78. Neither are present in normal kidneys. Activin inhibition with follistatin and neutralization of cell-surface GRP78 using a specific antibody blocked RhoA activation in mesangial cells and in diabetic kidneys. These data identify two novel RhoA/ROCK activators in diabetic kidneys that can be evaluated for their efficacy in inhibiting the progression of DKD. Full article
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
Role of Rho GTPase Interacting Proteins in Subcellular Compartments of Podocytes
Int. J. Mol. Sci. 2021, 22(7), 3656; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073656 - 01 Apr 2021
Viewed by 270
Abstract
The first step of urine formation is the selective filtration of the plasma into the urinary space at the kidney structure called the glomerulus. The filtration barrier of the glomerulus allows blood cells and large proteins such as albumin to be retained while [...] Read more.
The first step of urine formation is the selective filtration of the plasma into the urinary space at the kidney structure called the glomerulus. The filtration barrier of the glomerulus allows blood cells and large proteins such as albumin to be retained while eliminating the waste products of the body. The filtration barrier consists of three layers: fenestrated endothelial cells, glomerular basement membrane, and podocytes. Podocytes are specialized epithelial cells featured by numerous, actin-based projections called foot processes. Proteins on the foot process membrane are connected to the well-organized intracellular actin network. The Rho family of small GTPases (Rho GTPases) act as intracellular molecular switches. They tightly regulate actin dynamics and subsequent diverse cellular functions such as adhesion, migration, and spreading. Previous studies using podocyte-specific transgenic or knockout animal models have established that Rho GTPases are crucial for the podocyte health and barrier function. However, little attention has been paid regarding subcellular locations where distinct Rho GTPases contribute to specific functions. In the current review, we discuss cellular events involving the prototypical Rho GTPases (RhoA, Rac1, and Cdc42) in podocytes, with particular focus on the subcellular compartments where the signaling events occur. We also provide our synthesized views of the current understanding and propose future research directions. Full article
Show Figures

Figure 1

Open AccessReview
Role of Rho in Salt-Sensitive Hypertension
Int. J. Mol. Sci. 2021, 22(6), 2958; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062958 - 15 Mar 2021
Viewed by 429
Abstract
A high amount of salt in the diet increases blood pressure (BP) and leads to salt-sensitive hypertension in individuals with impaired renal sodium excretion. Small guanosine triphosphatase (GTP)ase Rho and Rac, activated by salt intake, play important roles in the pathogenesis of salt-sensitive [...] Read more.
A high amount of salt in the diet increases blood pressure (BP) and leads to salt-sensitive hypertension in individuals with impaired renal sodium excretion. Small guanosine triphosphatase (GTP)ase Rho and Rac, activated by salt intake, play important roles in the pathogenesis of salt-sensitive hypertension as key switches of intracellular signaling. Focusing on Rho, high salt intake in the central nervous system increases sodium concentrations of cerebrospinal fluid in salt-sensitive subjects via Rho/Rho kinase and renin-angiotensin system activation and causes increased brain salt sensitivity and sympathetic nerve outflow in BP control centers. In vascular smooth muscle cells, Rho-guanine nucleotide exchange factors and Rho determine sensitivity to vasoconstrictors such as angiotensin II (Ang II), and facilitate vasoconstriction via G-protein and Wnt pathways, leading to increased vascular resistance, including in the renal arteries, in salt-sensitive subjects with high salt intake. In the vascular endothelium, Rho/Rho kinase inhibits nitric oxide (NO) production and function, and high salt amounts further augment Rho activity via asymmetric dimethylarginine, an endogenous inhibitor of NO synthetase, causing aberrant relaxation and increased vascular tone. Rho-associated mechanisms are deeply involved in the development of salt-sensitive hypertension, and their further elucidation can help in developing effective protection and new therapies. Full article
Show Figures

Figure 1

Back to TopTop