A novel podocyte protein, R3h domain containing-like, inhibits TGF-β-induced p38 MAPK and regulates the structure of podocytes and glomerular basement membrane

Not only in kidney glomerular physiological function but also glomerular pathology especially in diabetic condition, glomerular podocytes play pivotal roles. Therefore, it is important to increase our knowledge about the genes and proteins expressed in podocytes. Recently, we have identified a novel podocyte-expressed gene, R3h domain containing-like (R3hdml) and analyzed its function in vivo as well as in vitro. Transforming growth factor-β (TGF-β) signaling regulated the expression of R3hdml. And R3hdml inhibited p38 mitogen-activated protein kinase phosphorylation, which was induced by TGF-β, leading to the amelioration of podocyte apoptosis. Furthermore, a lack of R3hdml in mice significantly worsened glomerular function in streptozotocin (STZ)-induced diabetes, while overexpression of R3hdml ameliorated albuminuria in STZ-induced diabetes. Our results surmise that the functional analyses of R3hdml may lead to the development of novel therapeutic strategies for diabetic nephropathy in the future. KEY MESSAGES: • A novel podocyte expressed protein R3h domain containing-like was identified. • R3HDML inhibits podocyte apoptosis by inhibiting TGF-β-mediated p38 MAPK signaling. • Overexpression of R3HDML ameliorates albuminuria in STZ-induced diabetes mice. • R3HDML may prove to be a novel therapeutic strategy for diabetic nephropathy.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:99

Enthalten in:

Journal of molecular medicine (Berlin, Germany) - 99(2021), 6 vom: 11. Juni, Seite 859-876

Sprache:

Englisch

Beteiligte Personen:

Ishikawa, Takahiro [VerfasserIn]
Takemoto, Minoru [VerfasserIn]
Akimoto, Yoshihiro [VerfasserIn]
Takada-Watanabe, Aki [VerfasserIn]
Yan, Kunimasa [VerfasserIn]
Sakamoto, Kenichi [VerfasserIn]
Maezawa, Yoshiro [VerfasserIn]
Suguro, Miyuki [VerfasserIn]
He, Liqun [VerfasserIn]
Tryggvason, Karl [VerfasserIn]
Betsholtz, Christer [VerfasserIn]
Yokote, Koutaro [VerfasserIn]

Links:

Volltext

Themen:

Apoptosis
Biomarkers
Diabetic nephropathy
EC 2.7.11.24
Journal Article
P38 Mitogen-Activated Protein Kinases
P38mapk
Podocyte
Research Support, Non-U.S. Gov't
TGF-β
Transforming Growth Factor beta

Anmerkungen:

Date Completed 18.01.2022

Date Revised 18.01.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s00109-021-02050-w

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM321789687