Fibroblast Growth Factor Type 2 Signaling Is Critical for DNA Repair in Human Keratinocyte Stem Cells

نویسندگان

  • Ghida Harfouche
  • Pierre Vaigot
  • Walid Rachidi
  • Odile Rigaud
  • Sandra Moratille
  • Mélanie Marie
  • Gilles Lemaitre
  • Nicolas O Fortunel
  • Michèle T Martin
چکیده

Tissue stem cells must be endowed with superior maintenance and repair systems to ensure genomic stability over multiple generations, which would be less necessary in more differentiated cells. We previously reported that human keratinocyte stem cells were more resistant to ionizing radiation toxicity than their direct progeny, the keratinocyte progenitor cells. In the present study we addressed the mechanisms underlying this difference. Investigations of DNA repair showed that both single and double DNA strand breaks were repaired more rapidly and more efficiently in stem cells than in progenitors. As cell signaling is a key regulatory step in the management of DNA damage, a gene profiling study was performed. Data revealed that several genes of the fibroblast growth factor type 2 (FGF2) signaling pathway were induced by DNA damage in stem cells and not in progenitors. Furthermore, an increased content of the FGF2 protein was found in irradiated stem cells, both for the secreted and the cellular forms of the protein. To examine the role of endogenous FGF2 in DNA repair, stem cells were exposed to FGF2 pathway inhibitors. Blocking the FGF2 receptor (FGF receptor 1) or the kinase (Ras-mitogen-activated protein kinase 1) resulted in a inhibition of single and double DNA strand-break repair in the keratinocyte stem cells. Moreover, supplementing the progenitor cells with exogenous FGF2 activated their DNA repair. We propose that, apart from its well-known role as a strong mitogen and prosurvival factor, FGF2 helps to maintain genomic integrity in stem cells by activating stress-induced DNA repair.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effect of Simulated Microgravity Conditions on Differentiation of Adipose Derived Stem Cells towards Fibroblasts Using Connective Tissue Growth Factor

Background: Mesenchymal stem cells (MSCs) are multipotent cells able to differentiating into a variety of mesenchymal tissues including osteoblasts, adipocytes and several other tissues. Objectives: Differentiation of MSCs into fibroblast cells in vitro is an attractive strategy to achieve fibroblast cell and use them for purposes such as regeneration medicine. The goal of this s...

متن کامل

The effect of Fibroblast Growth Factor-2(FGF-2) and retinoic acid on differentiation of mouse embryonic stem cells into neural cells

Introduction: Embryonic Stem (ES) cells as pluripotent cells derived from the inner cell mass of blastula can differentiate to neural cells in vitro and this property is valuable in studies of neurogenesis and in the generation of donor cells for transplantation. In this regard, the propose of this research, was the study of the role of two important factors in the development of neural syst...

متن کامل

Transdifferentiation of Human Dental Pulp Stem Cells Into Oligoprogenitor Cells

Introduction: The nerve fibers in central nervous system are surrounded by myelin sheet  which is formed by oligodendrocytes. Cell therapy based on oligodendrocytes and their precursors transplantation can hold a promising alternative treatment for myelin sheet repair in demyelinating diseases. Methods: Human Dental Pulp Stem Cells (hDPSCs) are noninvasive, autologous and easy available s...

متن کامل

Hepatocyte growth factor, keratinocyte growth factor, their receptors, fibroblast growth factor receptor-2, and the cells of the cornea.

PURPOSE The purpose of this study was to determine whether messenger RNA coding for hepatocyte growth factor (HGF), HGF receptor (MET), keratinocyte growth factor (KGF), KGF receptor, and fibroblast growth factor (FGF) receptor-2 were produced in primary cultures of human corneal epithelial, stromal fibroblast, and endothelial cells, as well as ex vivo corneal epithelium, endothelial cells tran...

متن کامل

Regulation of Bone Metabolism

Bone is formed through the processes of endochondral and intramembranous ossification. In endochondral ossification primary mesenchymal cells differentiate to chondrocytes and then are progressively substituted by bone, while in intramembranous ossification mesenchymal stem cells (MSCs) differentiate directly into osteoblasts to form bone. The steps of osteogenic proliferation, differentiation,...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 28  شماره 

صفحات  -

تاریخ انتشار 2010