HIFs in hypoxic regulation of the extracellular matrix:focus on little-known player HIF-3

The structural and associated molecules of the extracellular matrix(ECM)complex is an important component of the local milieu of cells,both for maintaining their functions and homeostasis.It is a dynamic structure that is finely tuned to changes in the microenvironment.One of these factors is hypoxia,which can arise in tissues due to physiological or pathological effects.As a result of the hypoxic effect,the properties of the ECM are significantly modified,stiffness increases,the balance between degradation and synthesis of structural proteins shifts,and the deposition of biologically active mediators’changes.Hypoxia-inducible factors(HIFs)contribute significantly to the modification of the properties of the ECM under hypoxia.Among the three HIF isoforms,HIF-1 is the most studied,with numerous identified target genes encoding proteins that participate in all matrisome compartments.Much less is known about HIF-2 and HIF-3.In the context of the effects of hypoxia on the matrisome,HIF-3 isoform is of particular interest.Unlike the first two isoforms,transiently expressed during the first hours of hypoxia,HIF-3 is activated after around 24 h of exposure to hypoxia and persists for a longer period.In addition,its transcription is more pronounced under hypoxia than are HIFs 1 and 2.HIF-3,rather than the first two isoforms,is possibly responsible for the changes that occur in matrisome during prolonged hypoxic conditions.This review attempts to summarize the available data on the involvement of HIF-3 in the matrisome modification under hypoxia.

Inflammatory priming of mesenchymal stem cells:Focus on growth factors enhancement

Multipotent mesenchymal stromal cells(MSCs)are actively involved in reparation and inflammation processes,providing damaged tissue reparation and suppressing immune cell responses in vivo.The effects are mostly due to the production of a wide range of paracrine factors,including growth factors and immunomodulatory mediators.To induce immunosuppressive activity,MSCs are primed by inflammatory cytokines,which results in an increased production of immunomodulatory molecules.However,stimulation of reparative properties is also necessary.This viewpoint manuscript highlights the possibilities of inflammatory priming to increase the production of growth factors by MSCs.