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Nicola Wilck

Publications and source records attributed to Nicola Wilck.

2 recordsLinked to original sources

Microbiota and kidney disease: the road ahead.

More than 850 million individuals worldwide, accounting for 10-15% of the adult population, are estimated to have chronic kidney disease. Each of these individuals is host to tens of trillions of microorganisms that are collectively referred to as microbiota - a dynamic ecosystem that both influences host health and is itself influenced by changes in the host. Available evidence supports the existence of functional connections between resident microorganisms and kidney health that are altered in the context of specific kidney diseases, including acute kidney injury, chronic kidney disease and renal stone disease. Moreover, promising data from preclinical studies suggest that targeting of gut microbial pathways may provide new therapeutic opportunities for the treatment of kidney disease. This Roadmap describes current understanding of the mechanisms by which microorganisms regulate host organ function, the effects of kidney disease on the gut microbiome, and how these insights may contribute to the development of microbe-targeted therapeutics. We highlight key knowledge gaps that remain to be addressed and strategies for addressing these, outlining both the promise and the potential pitfalls of leveraging our understanding of the gut microbiota to better understand and treat kidney disease.

Humans↗

Identification of estrogen receptor ligands leading to activation of non-genomic signaling pathways while exhibiting only weak transcriptional activity.

Estrogen receptors (ERs) stimulate genomic effects by acting as nuclear transcription factors as well as non-genomic effects by activating distinct cytoplasmic protein kinase cascades. Non-genomic effects have been implicated in numerous cellular processes, such as proliferation, differentiation, apoptosis and vasorelaxation. To exploit non-genomic effects mediated by ERalpha for novel hormone replacement regimens, we screened a focused library of steroid receptor ligands to identify compounds exhibiting properties different from estradiol, i.e. substances that selectively stimulate non-genomic signal transduction pathways while exhibiting low genomic activities. Treatment of breast cancer cells and osteosarcoma cells with estradiol, estren, substance A and substance B led to non-genomic activation of Akt (protein kinase B) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascades mediated by Src (Rous Sarcoma Virus, non-receptor tyrosine kinase) and phosphatidylinositol-3-kinase (PI3K) stimulation. Such compounds leading to prominent Akt/ERK activation but exhibiting only weak genomic properties were applied in vasorelaxation assays, modeling physiological non-genomic ER responses. As expected from PI3K and Src activation data, substances were as effective as estradiol in mediating vasorelaxation. We assume that these pathway-selective estrogen receptor ligands may serve as potent lead structures for novel hormone replacement strategies exhibiting lesser side effects than the existing treatment paradigms.

Animals↗