• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo

c-Met as a new marker of cellular senescence

c-met protein cellular senescence marker

  • Please log in to reply
No replies to this topic

#1 Engadin

  • Guest
  • 198 posts
  • 580
  • Location:Madrid
  • NO

Posted 16 May 2019 - 04:46 PM


Published at Rejuvenation Science News

 

 

Abstract

Here, we reported for the first time an increased expression of c-Met protein in primary cultures of human dermal and pulmonary fibroblasts of late passages. This suggests that c-Met could serve as an early marker of cellular senescence (CS). The levels of c-Met-related signaling proteins phospho-Akt and Stat3 were also increased in (pre)senescent fibroblasts. Considering the anti-apoptotic activity of Akt and the involvement of Stat3 in mediating the effects of proinflammatory cytokines, the findings of this study indicate that c-Met could contribute through its downstream targets or partners to at least two major phenotypical features of CS – resistance to apoptosis and senescence-associated secretory phenotype.

 

 
Introduction

 

In the last years, the phenomenon of cellular senescence (CS) has been becoming a hot topic in biomedical research. Apart from being involved in tissue repair upon wound healing [1,2] and acute fibrosis [3,4], cell reprogramming [5], and tissue remodeling during embryonic development [610], CS has attracted lots of attention, first and foremost, due to its strong links with aging and age-related diseases [11,12]. Indeed, the growing body of evidence indicates that accumulation of senescent cells could be an important player in mechanisms of aging and late-onset pathologies [1316]. Senescent cells are characterized by a stable cell growth arrest, enlarged, flattened shape of heterogenous morphology, resistance to apoptosis, secretion of a plethora of proinflammatory and ECM-modifying compounds, and expression of several molecular markers (e.g., p16INK4a, p21Cip1/Waf1, SA-β-gal, etc.) [17]. Yet, none of the existing molecular markers is exclusively indicative of CS, and there are ongoing attempts for reliable identification of senescent cells [18,19].

While searching for microRNAs with a potential involvement in CS, we observed a profound down-regulation of miR-199a-3p and miR-34a in pre-senescent human skin fibroblasts [20]. Among their experimentally validated targets is the hepatocyte growth factor receptor (MET), a well-known proto-oncogene encoding for the c-Met protein with tyrosine kinase activity [21]. Then, it would be reasonable to suggest that a decreased expression of miR-199a-3p and miR-34a in (pre)senescent cells could result in overexpression of c-Met. Indeed, elevated levels of c-Met were reported for a variety of tumors in which the members of miR-34 and miR-199 families are often silenced (reviewed by [22]). Not surprisingly, c-Met has extensively been studied in cancer research [21]. The studies on c-Met with regard to CS are fully absent.

The c-Met receptor can interact with a number of signaling proteins. As a result, this interaction may lead to induction of various signaling pathways (PI3K/AKT, JAK/STAT, etc.), thus explaining a wide range of c-Met biological activities including cell survival, migration and adhesion [21,23,24]. Of note, all of these activities could be relevant to CS.

This study was undertaken to evaluate whether the expression of c-Met is altered in the course of replicative CS, and if so, whether its levels could serve as a new marker of senescent cells. Also, to get insight into possible role of c-Met in CS, we determined the expression of its downstream targets Akt and Stat3.

 

 

.....

 

 

F U L L   T E X T :   Nature - Molecular Psychiatry

 


Edited by Engadin, 16 May 2019 - 05:03 PM.






Also tagged with one or more of these keywords: c-met protein, cellular senescence, marker

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users