Podocyte A20/TNFAIP3 Controls Glomerulonephritis Severity via the Regulation of Inflammatory Responses and Effects on the Cytoskeleton

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10496061" target="_blank" >RIV/00064203:_____/25:10496061 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/25:10496061

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=XDpBToJQ3F" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=XDpBToJQ3F</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells14050381" target="_blank" >10.3390/cells14050381</a>

Result language

angličtina

Original language name

Podocyte A20/TNFAIP3 Controls Glomerulonephritis Severity via the Regulation of Inflammatory Responses and Effects on the Cytoskeleton

Original language description

A20/Tnfaip3, an early NF-κB response gene and key negative regulator of NF-κB signaling, suppresses proinflammatory responses. Its ubiquitinase and deubiquitinase activities mediate proteasomal degradation within the NF-κB pathway. This study investigated the involvement of A20 signaling alterations in podocytes in the development of kidney injury. The phenotypes of A20Δpodocyte (podocyte-specific knockout of A20) mice were compared with those of control mice at 6 months of age to identify spontaneous changes in kidney function. A20Δpodocyte mice presented elevated serum urea nitrogen and creatinine levels, along with increased accumulation of inflammatory cells-neutrophils and macrophages-within the glomeruli. Additionally, A20Δpodocyte mice displayed significant podocyte loss. Ultrastructural analysis of A20 podocyte-knockout mouse glomeruli revealed hypocellularity of the glomerular tuft, expansion of the extracellular matrix, podocytopenia associated with foot process effacement, karyopyknosis, micronuclei, and podocyte detachment. In addition to podocyte death, we also observed damage to intracapillary endothelial cells with vacuolation of the cytoplasm and condensation of nuclear chromatin. A20 expression downregulation and CRISPR-Cas9 genome editing targeting A20 in a podocyte cell line confirmed these findings in vitro, highlighting the significant contribution of A20 activity in podocytes to glomerular injury pathogenesis. Finally, we analyzed TNFAIP3 transcription levels alongside genes involved in apoptosis, anoikis, NF-κB regulation, and cell attachment in glomerular and tubular compartments of kidney biopsies of patients with various renal diseases.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30101 - Human genetics

Project

<a href="/en/project/NV19-06-00443" target="_blank" >NV19-06-00443: Genetics of adult-onset familial focal segmental glomerulosclerosis (FSGS) – implications for individualized therapy and successful kidney transplantation</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cells

ISSN

2073-4409

e-ISSN

2073-4409

Volume of the periodical

14

Issue of the periodical within the volume

5

Country of publishing house

CH - SWITZERLAND

Number of pages

24

Pages from-to

381

UT code for WoS article

001442293700001

EID of the result in the Scopus database

2-s2.0-86000493041