Scientists are closer to understanding the development of chronic bladder diseases which could lead to more effective medicines for patients.
The inside of the bladder is lined with a layer of tissue called the urothelium. This lining regenerates and acts as a barrier between urine and healthy cells.
In chronic bladder disease, the regenerative function of the urothelium is often disrupted which makes it unable to carry out its normal job.
This process of regeneration is dictated by the activation and suppression of specific parts of a person’s DNA by molecules called transcription factors (TFs). It is the disruption of these TFs that leads to chronic bladder diseases.
Researchers used human cells to grow urothelial tissue in a lab. Individual TFs were then individually ‘silenced’ one at a time to understand what effect they were having on the state of the urothelium.
The team took note of the way different TFs would interact with DNA, finding out which TFs interacted when and how their individual interactions would be influenced by other TFs.
Researchers discovered that TFs interacted with DNA sequences in a non-hierarchical fashion, i.e., each TF had the same authority as other TFs.
Cell biology is built on the fundamental understanding that specific molecules have specific effects on cell function. Thanks to years of clinical research, many of these molecular interactions have been mapped out.
For a lot of cell functions, molecular interactions exist as signaling pathways – a distinct sequence of molecules interacting with other molecules to cause an end result. With this in-depth knowledge of cell interactions, treatments can be targeted to interfere with specific molecules to give a more powerful medicinal benefit.
Knowing how TFs interact with DNA in urothelial cells helps scientists understand the beginnings and development of chronic bladder diseases.
Fishwick C, Higgins J, Percival-Alwyn L, Hustler A, Pearson J, Bastkowski S, Moxon S, Swarbreck D, Greenman CD, Southgate J. Heterarchy of transcription factors driving basal and luminal cell phenotypes in human urothelium. Cell Death Differ 2017; 24:809-818.
- Southgate J, Hutton KA, Thomas DF, Trejdosiewicz LK. Normal human urothelial cells in vitro: proliferation and induction of stratification. Lab Invest 1994; 71:583-94.