The role of Cdc42 protein in the regulation of mesenchymal stem cells senescence

The role of Cdc42 protein in the regulation of mesenchymal stem cells senescence

IRN AP08856264

 

Introduction: Our previous results indicate that Cdc42 activity showed an age-related increase in mesenchymal stem cells (MSCs) from adipose tissue of rats and pharmacological reduction of Cdc42 activity can reverse the aging process in mesenchymal stem cells. The mechanisms how Cdc42 regulates cell senescence is unclear. This may be due to the regulation of active oxygen generation. For example, we showed that the level of ROS was increased in an age-related manner in rat adipose-derived mesenchymal stem cells and inhibition of Cdc42 activity reduced oxidative stress. There are a number of possible mechanisms underlying this regulation, including activation of NADPH oxidase (NOX) as most likely downstream effector of Cdc42 mediated ROS induction. We hypothesize that elevated level of Cdc42 in aged MSCs induces activation of NOX and ROS accumulation through actin filament reorganization. Therefore, in this project, we have focused on molecular mechanisms contributing to mesenchymal stem cell aging associated with Cdc42 and the role of NADPH oxidase as a downstream effector of Cdc42 mediated aging.

Goal: is to study the molecular mechanisms contributing to mesenchymal stem cell aging associated with Cdc42 and oxidative stress.

Expected results:

The effects of inhibition of Cdc42 on NADPH oxidase, reactive oxygen species, actin polymerization and senescence-related markers in aged rat adipose-derived mesenchymal stem (ADMSCs) cells will be studied.  The effects of activation of Cdc42 on NADPH oxidase, reactive oxygen species, actin polymerization, senescence-related markers and osteogenic differentiation in ADMSs will be evaluated.  at least 3 (three) articles and (or) reviews in peer-reviewed scientific journals in the scientific filed of the project, included in 1 (first), 2 (second) or 3 (third) quartiles in the Web of Science database and (or) having a percentile by CiteScore in the Scopus database of at least 50 (fifty) will be published (presumable journals: Oxidative medicine and cellular longevity (CiteScore 2019 -7.3, percentile – 83, journal H Index -79, Quartiles –Q2 (Aging), IF-4.58, https://www.scimagojr.com/journalsearch.php?q=19700175026&tip=sid; Stem Cells International (CiteScore2019 -7.200, H- Index -55,IF- 3.869, )https://www.scimagojr.com/journalsearch.php?q=19900191989&tip=sid&clean=0); - and at least 1 (one) article in a peer-reviewed foreign and (or) domestic journal with a non-zero impact factor (recommended by CQAEA).

Current results:

The effects of inhibition of Cdc42 on NADPH oxidase, reactive oxygen species, actin polymerization and senescence-related markers in aged rat adipose-derived mesenchymal stem (ADMSCs) cells were studied. The results obtained in 2021 indicate that the expressions of NADPH oxidase isoforms: NOX1 and NOX4 in aged rat adipose-derived mesenchymal stem were increased. In turn, inhibition and silencing of Cdc42 lead to the normalization of the expression of these isoforms, a decrease in oxidative stress and actin polymerization, and an improvement in markers of cell aging.

 

Research group:

Full name

Identifier

Links

Umbayev Bauyrzhan, PhD  

Scopus Author ID:  26327096700

 

ORCID: 0000-0002-0286-7252

 

Web of Science ResearcherID: AAR-1900-2020

https://www.scopus.com/authid/detail.uri?authorId=26327096700

 

https://orcid.org/0000-0002-0286-7252

 

https://www.webofscience.com/wos/author/record/5709931

 

 

Olzhayev Farkhad, MD

Scopus Author ID:  56605070400

ORCID: 0000- 0000-0002-1906-6654

 

Web of Science ResearcherID: P-2121-2015

 

https://www.scopus.com/authid/detail.uri?authorId=56605070400

 

https://orcid.org/0000-0002-1906-6654

 

 

 

https://www.webofscience.com/wos/author/record/8052262

 

Tsoy Andrey, PhD

Scopus Author ID:56362596800

 

 

Web of Science Researcher ID:

K-3983-2014

https://www.scopus.com/authid/detail.uri?authorId=56362596800

 

https://publons.com/researcher/2494656/andrey-tsoy/

 

Safarova Yuliya, Phd,

Scopus Author ID: 57216161697

 

ORCID: 0000-0003-0695-0413

 

Web of Science Researcher ID: AAL-7843-2020

https://www.scopus.com/authid/detail.uri?authorId=57216161697

 

 

https://orcid.org/0000-0003-0695-0413

 

 

https://www.webofscience.com/wos/author/record/35509508

 

Yermekova Aislu

 

 

 

Publications in 2021: No