Osr1 Is Required for Mesenchymal Derivatives That Produce Collagen in the Bladder.

Vasikar Murugapoopathy,Lysanne Campeau,Philippe G Cammisotto,Abubakr H Mossa,Indra R Gupta

doi:10.3390/ijms222212387

Abstract

The extracellular matrix of the bladder consists mostly of type I and III collagen, which are required during loading. During bladder injury, there is an accumulation of collagen that impairs bladder function. Little is known about the genes that regulate production of collagens in the bladder. We demonstrate that the transcription factor Odd-skipped related 1 (Osr1) is expressed in the bladder mesenchyme and epithelium at the onset of development. As development proceeds, Osr1 is mainly expressed in mesenchymal progenitors and their derivatives. We hypothesized that Osr1 regulates mesenchymal cell differentiation and production of collagens in the bladder. To test this hypothesis, we examined newborn and adult mice heterozygous for Osr1, Osr1+/−. The bladders of newborn Osr1+/− mice had a decrease in collagen I by western blot analysis and a global decrease in collagens using Sirius red staining. There was also a decrease in the cellularity of the lamina propria, where most collagen is synthesized. This was not due to decreased proliferation or increased apoptosis in this cell population. Surprisingly, the bladders of adult Osr1+/− mice had an increase in collagen that was associated with abnormal bladder function; they also had a decrease in bladder capacity and voided more frequently. The results suggest that Osr1 is important for the differentiation of mesenchymal cells that give rise to collagen-producing cells.

Highlights

The bladder is a hollow sac that stores urine and can expand up to three to four times its size when full
At postnatal (P) day 1, Odd-skipped related 1 (Osr1) expression was detected in almost all cells in the lamina propria and epithelia, and some cells in the muscle layer
The amount of cell proliferation in the bladder was similar at both timepoints when comparing Osr1+/− and Osr1+/+ embryos and newborn pups (Figur5eof31)2. These results suggest that the loss of cellularity in the lamina propria layer could be due to a defect in mesenchymal cell differentiation

Summary

Introduction

The bladder is a hollow sac that stores urine and can expand up to three to four times its size when full. The contractions are coordinated by three primary layers: the epithelial layer, the lamina propria, and the muscle layer. The latter two layers are rich in extracellular matrix. The bladder wall becomes thicker with a marked increase in ECM in the lamina propria and muscle [6,7,8,9]. This results in a high-pressure bladder that is stiff and unable to empty. Patients with this bladder dysfunction require intermittent catheterization to maintain urinary continence

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Conclusion