From Nucleus to Organs: Insights of Aryl Hydrocarbon Receptor Molecular Mechanisms.

The aryl hydrocarbon receptor (AHR) is a markedly established regulator of a plethora of cellular and molecular processes. Its initial role in the detoxification of xenobiotic compounds has been partially overshadowed by its involvement in homeostatic and organ physiology processes. In fact, the discovery of its ability to bind specific target regulatory sequences has allowed for the understanding of how AHR modulates such processes. Thereby, AHR presents functions in transcriptional regulation, chromatin architecture modifications and participation in different key signaling pathways. Interestingly, such fields of influence end up affecting organ and tissue homeostasis, including regenerative response both to endogenous and exogenous stimuli. Therefore, from classical spheres such as canonical transcriptional regulation in embryonic development, cell migration, differentiation or tumor progression to modern approaches in epigenetics, senescence, immune system or microbiome, this review covers all aspects derived from the balance between regulation/deregulation of AHR and its physio-pathological consequences.

Liver regeneration after partial hepatectomy is improved in the absence of aryl hydrocarbon receptor.

The liver is among the few organs having the ability to self-regenerate in response to a severe damage compromising its functionality. The Aryl hydrocarbon receptor (Ahr) is a transcription factor relevant for the detoxification of xenobiotics but also largely important for liver development and homeostasis. Hence, liver cell differentiation is developmentally modulated by Ahr through the controlled expression of pluripotency and stemness-inducing genes. Here, 2/3 partial hepatectomy (PH) was used as a clinically relevant approach to induce liver regeneration in Ahr-expressing (Ahr+/+) and Ahr-null (Ahr-/-) mice. Ahr expression and activity were early induced after 2/3 PH to be gradually downmodulated latter during regeneration. Ahr-/- mice triggered liver regeneration much faster than AhR+/+ animals, although both reached full regeneration at the latest times. At initial stages after PHx, earlier regenerating Ahr-/- livers had upregulation of cell proliferation markers and increased activation of signalling pathways related to stemness such as Hippo-YAP and Wnt/ß-catenin, concomitantly with the induction of pro-inflammatory cytokines TNFa, IL6 and p65. These phenotypes, together with the improved metabolic adaptation of Ahr-/- mice after PHx and their induced sustained cell proliferation, could likely result from the expansion of undifferentiated stem cells residing in the liver expressing OCT4, SOX2, KLF4 and NANOG. We propose that Ahr needs to be induced early during regeneration to fine-tune liver regrowth to physiological values. Since Ahr deficiency did not result in liver overgrowth, its transient pharmacological inhibition could serve to improve liver regeneration in hepatectomized and transplanted patients and in those exposed to damaging liver toxins and carcinogens.

The importance of marshes providing soil stabilization to resist fast-flow erosion in case of a dike breach.

Salt marshes provide valuable ecosystem services including coastal protection by reducing wave loading on dikes and seawalls. If the topsoil is erosion resistant to fast-flowing water, it may also reduce breach depth if a dike fails. In this experiment, we quantified the topsoil erosion resistance from marshes and bare tidal flats with different soil types to understand the extent to which they can help reduce breach depth. Intact soil samples were collected from 11 locations in the Netherlands at different tidal elevations and then exposed for 3 h to 2.3 m/s currents. To the samples that remained stable after flow exposure, an artificial crack was made to test their stability following soil disturbance. All samples from the tidal flats were completely eroded, regardless of sediment type. In contrast, all samples from well-established marsh plateaus were stable as long as no disturbances were made, including those with sandy subsoils. After creating artificial cracks, samples with a thin cohesive top layer on top of sandy subsoil collapsed, while marshes with silty subsoils remained stable. Pioneer marshes on sandy substrate without a cohesive top layer were the only vegetated soils that completely eroded. The lower erosion of marshes with either sandy or silty soils compared to bare tidal flats was best explained by the presence of a top layer with belowground biomass, high organic content, high water content, and low bulk density. When analyzing the erodibility of marshes only, fine root density was the best predictor of erosion resistance. This study demonstrates the importance of preserving, restoring, or creating salt marshes, to obtain a topsoil that is erosion resistant under fast-flowing water, which helps reduce breach dimensions if a dike fails. The probability of topsoil erosion in established marshes with sandy subsoil is higher than in silty marshes. A silty layer of cohesive sediment on top of the sand provides extra erosion resistance as long as it does not break. Pioneer marshes that have not developed a cohesive top layer are erosion sensitive, especially in sandy soils. For future marsh creations, using fine-grained sediments or a mixture of sand with silt or clay is recommended.