Role of Rho GTPase Interacting Proteins in Subcellular Compartments of Podocytes

Asano-Matsuda, Kana; Şehitoğlu, İbrahim; Takano, Tomoko; Matsuda, Jun

doi:10.3390/ijms22073656

Cited by 11 publications

(7 citation statements)

References 92 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well established that the correct function of glomerular filtration relies on podocyte adhesion both at the interface with the extracellular membrane and at cell junctions [ 37 ]. The Rho family of small GTPases (Rho GTPases) closely regulates actin cytoskeleton and performs diverse cellular functions such as adhesion, migration and spreading in podocytes [ 38 ]. ARHGEF5, a member of the Rho guanine nucleotide exchange factor (GEF), is induced during the TGF-β-induced mesenchymal transition of endothelial cells [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma Exosomal Non-Coding RNA Profile Associated with Renal Damage Reveals Potential Therapeutic Targets in Lupus Nephritis

Flores-Chova

Martínez-Arroyo

Riffo‐Campos

et al. 2023

IJMS

View full text Add to dashboard Cite

Despite considerable progress in our understanding of systemic lupus erythematosus (SLE) pathophysiology, patient diagnosis is often deficient and late, and this has an impact on disease progression. The aim of this study was to analyze non-coding RNA (ncRNA) packaged into exosomes by next-generation sequencing to assess the molecular profile associated with renal damage, one of the most serious complications of SLE, to identify new potential targets to improve disease diagnosis and management using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The plasma exosomes had a specific ncRNA profile associated with lupus nephritis (LN). The three ncRNA types with the highest number of differentially expressed transcripts were microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and piwi-interacting RNAs (piRNAs). We identified an exosomal 29-ncRNA molecular signature, of which 15 were associated only with LN presence; piRNAs were the most representative, followed by lncRNAs and miRNAs. The transcriptional regulatory network showed a significant role for four lncRNAs (LINC01015, LINC01986, AC087257.1 and AC022596.1) and two miRNAs (miR-16-5p and miR-101-3p) in network organization, targeting critical pathways implicated in inflammation, fibrosis, epithelial–mesenchymal transition and actin cytoskeleton. From these, a handful of potential targets, such as transforming growth factor-β (TGF-β) superfamily binding proteins (activin-A, TGFB receptors, etc.), WNT/β-catenin and fibroblast growth factors (FGFs) have been identified for use as therapeutic targets of renal damage in SLE.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasma Exosomal Non-Coding RNA Profile Associated with Renal Damage Reveals Potential Therapeutic Targets in Lupus Nephritis

Flores-Chova

Martínez-Arroyo

Riffo‐Campos

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Gelsolin levels increased significantly as PAN concentration increased (* p < 0.05; Fig- ure 4C). RhoA and Rac1 are Rho GTPases that regulate a variety of cell behaviors, including actin dynamics [16,17]. Additionally, the expression of RhoA and Rac1 increased in proportion to the PAN concentration (Figure 4D,E).…”

Section: Gelsolin Expression Increased In Pan-damaged Podocytesmentioning

confidence: 99%

The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes

Damaiyanti

Yan

et al. 2021

IJMS

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is normally related to proteinuria, a common finding in a compromised glomerular filtration barrier (GFB). GFB is a structure composed of glomerular endothelial cells, the basement membrane, and the podocytes. CKD with podocyte damage may be associated with actin cytoskeleton reorganization, resulting in podocyte effacement. Gelsolin plays a critical role in several diseases, including cardiovascular diseases and cancer. Our current study aimed to determine the connection between gelsolin and podocyte, and thus the mechanism underlying podocyte injury in CKD. Experiments were carried out on Drosophila to demonstrate whether gelsolin had a physiological role in maintaining podocyte. Furthermore, the survival rate of gelsolin-knocked down Drosophila larvae was extensively reduced after AgNO3 exposure. Secondly, the in vitro podocytes treated with puromycin aminonucleoside (PAN) enhanced the gelsolin protein expression, as well as small GTPase RhoA and Rac1, which also regulated actin dynamic expression incrementally with the PAN concentrations. Thirdly, we further demonstrated in vivo that GSN was highly expressed inside the glomeruli with mitochondrial dysfunction in a CKD mouse model. Our findings suggest that an excess of gelsolin may contribute to podocytes damage in glomeruli.

show abstract

“…Endothelial barrier regulation is dependent on the cytoskeletal rearrangements (Vogel and Malik, 2012). The small Rho GTPases, RhoA, and Rac1, are central regulators of vascular permeability through cytoskeletal reorganization (Asano-Matsuda et al, 2021). RhoA and Rac1 exert opposing functional Besides, Rap1 GTPase is also involved in the regulation of cytoskeleton and cell junctions.…”

Section: Rho Gtpase-yap/tazmentioning

confidence: 99%

Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung

et al. 2022

View full text Add to dashboard Cite

Mechanical stress plays a critical role among development, functional maturation, and pathogenesis of pulmonary tissues, especially for the alveolar epithelial cells and vascular endothelial cells located in the microenvironment established with vascular network and bronchial-alveolar network. Alveolar epithelial cells are mainly loaded by cyclic strain and air pressure tension. While vascular endothelial cells are exposed to shear stress and cyclic strain. Currently, the emerging evidences demonstrated that non-physiological mechanical forces would lead to several pulmonary diseases, including pulmonary hypertension, fibrosis, and ventilation induced lung injury. Furthermore, a series of intracellular signaling had been identified to be involved in mechanotransduction and participated in regulating the physiological homeostasis and pathophysiological process. Besides, the communications between alveolar epithelium and vascular endothelium under non-physiological stress contribute to the remodeling of the pulmonary micro-environment in collaboration, including hypoxia induced injuries, endothelial permeability impairment, extracellular matrix stiffness elevation, metabolic alternation, and inflammation activation. In this review, we aim to summarize the current understandings of mechanotransduction on the relation between mechanical forces acting on the lung and biological response in mechanical overloading related diseases. We also would like to emphasize the interplays between alveolar epithelium and vascular endothelium, providing new insights into pulmonary diseases pathogenesis, and potential targets for therapy.

show abstract

Role of Rho GTPase Interacting Proteins in Subcellular Compartments of Podocytes

Cited by 11 publications

References 92 publications

Plasma Exosomal Non-Coding RNA Profile Associated with Renal Damage Reveals Potential Therapeutic Targets in Lupus Nephritis

Plasma Exosomal Non-Coding RNA Profile Associated with Renal Damage Reveals Potential Therapeutic Targets in Lupus Nephritis

The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes

Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung

Contact Info

Product

Resources

About