PhD Scientific Days 2025

Poster Session II. - J: Theoretical and Translational Medicine

The Role of the Small GTPase RhoA in the Human Detrusor Muscle

Előadó neve

Balla Helga

Előadó munkahelye

Institute of Translational Medicine, Semmelweis University

Előadó telefonszáma

+36301617621

Előadó e-mail címe

helgaballa1996@gmail.com

Az előadás címe

The Role of the Small GTPase RhoA in the Human Detrusor Muscle

Szerző(k) neve és munkahelye

Helga Balla^1,2, Kinga Borsodi^1,2, Péter József Molnár³, Ádám Lénárt³, Dejan Dobi⁴, András Budai⁴, András Horváth³, Attila Keszthelyi³, Miklós Romics³, Attila Majoros³, Péter Nyirády³, Stefan Offermanns⁵, Zoltán Benyó^1,2

1: Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.
2: HUN-REN-SU Cerebrovascular and Neurocognitive Disease Research Group, Budapest, Hungary.
3: Department of Urology, Semmelweis University, Budapest, Hungary.
4: Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.
5: Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.

Bemutatás módja

Poszter

Szekció

Poster Session II. - J: Theoretical and Translational Medicine

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Overactive bladder (OAB) is a common clinical condition with a prevalence of 16 %. Currently, antimuscarinic drugs are the first-line medical therapy for the management of OAB. However, their application is limited due to several side effects (e.g., dry mouth, obstipation). Our previous results show that ROCK is pivotal in regulating contractions in murine and human urinary bladder (UB).
We aimed to analyze further the role of the small GTPase RhoA in the intracellular signaling of the human urinary bladder smooth muscle (UBSM) contraction. Our final goal is to provide novel, more specific therapeutic targets for OAB.
Experiments were performed on surgically removed human UBs due to bladder malignancy. UBSM strips were dissected from a tumor-free area, approved by a pathologist, before being mounted on a myograph. After that, the strips were challenged with different agonists [10-5 M, carbachol (CCh), bradykinin (BK), neurokinin A (NKA)]. RhoA activity was measured in the human UBSM. Pharmacological pretreatment was applied depending on the experiment.
Our results show that CCh increased the activity of RhoA in the human UBSM compared to the control group. In addition, the CCh-induced RhoA activation was diminished in the presence of atropine. The effect of carbachol on RhoA activity was found to be abolished in detrusor strips treated with the M2 receptor antagonist AF-DX 16. The M3 receptor inhibitor 4-DAMP did not modify the CCh-induced RhoA activity. Next, we wanted to investigate the role of the inflammatory mediator BK in RhoA activation in human UB. BK evoked an increase in RhoA activity moreover, the BK-induced RhoA activation was diminished in human UBSM tissues treated with the B2 receptor inhibitor HOE-140. Finally, the RhoA activity induced by NKA was reduced in UBSM treated with the NK2 receptor antagonist MEN-10376.
We summarized that the RhoA-ROCK pathway plays an essential role in the human UBSM. Moreover, CCh-induced RhoA activation is mediated mostly by the M2 muscarinic receptors. In addition, RhoA activation induced by BK or NKA is transmitted mostly by the B2 or NK2 receptors, respectively. The detailed understanding of the RhoA-ROCK pathway in the human UB may offer a novel, more specific target in the treatment of OAB with fewer side effects.
K-135683, K-139230, PD-143327; EKÖP-2024-37 and TKP2021-EGA-25 from the Hungarian NRDIO

University

Semmelweis University

Supervisor

Zoltán Benyó

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

after finishing doctoral studies with absolutorium (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6178

Start

18:24

End

18:30