Oxygen and miRNAs in Cosmetology and Dermatology

A recent review by Nadim et al. casts some light on a Cosmetology and Dermatology, where circulating biomarkers, though studied to a certain extent so far, are yet unknown for many skin models. (1) A first element to have in mind when considering the skin-related experimental model is the “Oxygen level”. Oxygen levels may contribute to different findings, and the in vitro models used so far may not be so physiologically relevant as initially thought.

Hypoxia and miRNAs

Tissue oxygenation (which is a major part of the cell microenvironment) regulates the expression of the microRNAs called oxymiRs. OxymiRs may be categorized into three groups:

  1. microRNAs whose expression is directly modied by the Oxygen partial pressure,
  2. microRNAs whose expression is indirectly (pH, metabolites, etc.) modified by the Oxygen partial pressure, andpO2 percentage levels in various tissues
  3. microRNAs that target mediators of Oxygen sensing pathways to regulate biological networks for cell survival.

Examples of miRNAs important in skin physiology include miR-17, miR-21, miR-24, miR-27, miR-29b, miR-99 family, miR-125, miR-146a, miR-155, miR-203 and miR-205, among many other.

For example, in injured tissue, disruption of the vascular supply is associated with a low oxygen partial pressure, or hypoxia, which induces the expression of specic microRNAs referred to as HypoxamiRs (included in group (1) of the oxymiRs classification).

miR-210, known as the master HypoxamiR, is robustly induced under hypoxic conditions in nearly all kinds of cells. Under hypoxia, miR-21 also induces angiogenesis by targeting PTEN, leading to activation of AKT and ERK1/2 signaling pathways.

Transfection Factors and microRNAs

Other transcription factors such as p53 and NF-kB have been shown to affect the expression of microRNAs under hypoxia/anoxia conditions.

Numerous studies have demonstrated the modulation of microRNA expression and particularly that of the miR-200 family with oxidative stress due to excessive ROS levels.

Up to now, very few studies have shown the role of the intermediate Oxygen level (physioxia) in regulating microRNA expression in skin cells. Taken together, these results strongly support the idea that physioxia should be an important criterion in determining the microRNA expression level and consequently protein expression and skin functions.

Therefore, when trying to understand the role of microRNAs in skin models, it is important to choose a cell culture system that is as physiological as possible, and have the tools to analyse the different biomarkers (no only microRNA, but also signaling pathways, secretome, etc).

Should you like to have more information on this review, or know what we can do for you to support you with cell culture technologies with controlled oxygen levels or to support you for your biomarker discovery studies, do not hesitate to contact me by leaving a message below.

Source:

(1) Nadim M. et al. “Physioxia and MicroRNAs As Key Factors in the Skin Microenvironment” (2015) FSCC Magazine, Vol. 18 – #1, pp: 35-43

5 most popular pathways in 2014!

Today, I’d like to invite you to take a look at the 5 posts describing a pathway that saw the most visits on our blog in 2014. 

Just follow the links if you haven’t read them yet (or if you want to browse them again, feel free!).

[Read more…]

miRNA and cytokine profiling in hypoxic adipose tissue

In a recent publication, Mennesson E. et al. have developped a smart approach to perform both adipokine protein and miRNA profilings in in vitro adipocyte models mimicking the physiological state of adipose tissues. Adipokines and miRNAs are now known to be involved in adipose tissue metabolism in obesity during which hypoxic adipose tissue development is seen due to tissue mass expansion. Such Cytokine and miRNA profilings are thus needed to better decipher the physiopathology of obesity and to identify new biomarkers.

[Read more…]

Physioxia or Hypoxia: what it’s all about

Cell culture under oxygen controlled conditions: an improvement towards more predictive results

Oxygen concentration in tissues is a key factor for cell and organ survival. In normal conditions, partial oxygen pressure (pO2) results in the balance between oxygen delivery and its consumption. Oxygen is transported, in mammals, by circulating red blood cells. Partial oxygen pressure in tissues varies widely, depending on their respective metabolic requirements and their functional status. In normal physiological conditions,  partial oxygen pressure is called physioxia. Any alteration of tissue environment leading to a decrease in partial oxygen pressure is called hypoxia. Hypoxic conditions have been observed in many different pathological situations like tumor development, obesity or transcient ischemia. [Read more…]

Focus on the Hypoxia Regulation Mechanism

The cellular and physiological effects resulting from hypoxia-dependent networks have been clearly shown to impact a number of human pathological states, including ischemic disease, diabetes, pulmonary disease and, perhaps most notably, cancer. Thus, further research into the biomedical effects of hypoxia could lead to novel therapeutic approaches for these diseases.

[Read more…]

Focus on the Hypoxia Pathway…

Hypoxia in tumors is closely associated with tumor aggressiveness and resistance to radio- and chemotherapeutic treatment. Therefore, reliable markers for hypoxia represent both valuable diagnostic markers and potential targets for investigation.

[Read more…]

PARP inhibitors are less synthetically lethal in hypoxic conditions – AACR 2014

Hypoxia has important effects on chemosensitivity of cancer cells and the synthetic lethal effects of drugs.

In a recent work presented during the “Experimental and Molecular Therapeutics” sessions at the AACR 2014, Claudine Kiéda’s and Nadia Normand’s teams showed that PARP inhibitors are less synthetically lethal in hypoxic conditions with increased IC50 and survival percentage at higher concentrations.

Synthetic Lethality (SL) is defined as when loss of two genes independently has no effect on viability, but simultaneous loss of both genes causes cell death.

In cancer research and drug discovery, SL is observed when the cancer mutation and the drug simultaneously inhibit two otherwise independent pathways, leading to cell death. The best known SL relationship is between BRCA1/2 mutation (tumors deficient in Homologous Recombination (HR) DNA Repair pathway) and PARP inhibitors (affecting the Base Excision Repair (BER) DNA Repair pathway).

In their work, Dr Kiéda and Dr Normand used already published in vitro stable BRCA1- and BRCA2-KD cell lines (SilenciX® technology) to measure the synthetic lethal efficiency of PARP inhibitors (Olaparib, Veliparib and Rucaparib) in both normoxic and hypoxic conditions. They demonstrate that the BRCA-KD SilenciX® cell lines are effective and convenient in vitro cellular models to design new cancer drug candidates through the SL approach in oxygen-controlled conditions to better mimick physioxia seen in solid tumors.

Sources:

SilenciX®, novel stable knock-down cellular models to screen new molecular targets through the synthetic lethality approach  (“Experimental and Molecular Therapeutics” poster session – AACR 2014, San Diego) Abstract n° 3733
Eric Mennesson1, Anne-Marie Renault1, Isabelle Fixe1, Catherine Grillon2, Claudine Kiéda2, Nadia Normand1  (1/ tebu-bio – 2/ Centre de Biophysique Moléculaire CNRS UPR 4301 (France)).

2 cost-effective antibody options for Hypoxia pathway analysis

Low oxygen tension, or Hypoxia, regulates numerous cellular and tissular functions. In cancer research, hypoxia is a key regulator of tumor development, aggressiveness and therapy resistance by acting on malignant cells and their microenvironment. Hypoxia is also involved in age-related diseases and acts through intracellular and intercellular cascade of events (exosomes, paracrine loops, angiogenesis…) (1-2). [Read more…]