Dynamically Urethra-Adapted and Obligations-Oriented Trilayer Hydrogels Integrate Scarless Urethral Repair
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1284280 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In urethral damage/stricture prevention, open and harsh urethral microenvironments as well as the isotropic compression and swelling properties of exogenous implants render urethral repair intractable. Here, a dynamically urethra-adapted and obligation-oriented trilayer hydrogel was constructed for integrated scarless urethral repair. The bottom diethylacrylamide -hydroxyethylacrylamide (D-H) hydrogel featuring high anti-fouling performance, the upper swellable verteporfin (VP)-loaded N,N'-methylenebisacrylamide-poly (N-isopropylacrylamide) (BP) with a hydrophilic Janus surface promote urethral regeneration through expediting cell migration and proliferation and the rigid and water-resistant Zein middle layer opposes urine voiding-arised BP shedding and resists inward BP swelling-driven urethral occlusion and urine permeation. Importantly, systematic proteomic and genomic analyses revealed that such hydrogel scaffolds expedite regeneration, alleviate inflammation and regulate extracellular matrix secretion, where BP swelling-induced outgrowth for fibrosis and scar formation is significantly inhibited by VP through the blockade of the scar-associated YAP signaling pathway. These microenvironment-adaptable design concepts provide a rationale for engineering urethral regeneration scaffolds.
2025-07-01 | GSE301213 | GEO
Project description:Penis, the organ that bears reproductive and psychological importance, is susceptible to birth defects such as hypospadias, or incomplete closure of urethra along the penis shaft. We discover that proper urethral closure in mouse embryos requires a unique mesenchymal cell population originated from outside of the penis. These “extra-genital” cells, marked by a lineage marker Nr5a1, migrate from the inguinal region into the embryonic penis, and facilitate urethra closure by interacting with adjacent peri-urethral cells via the epidermal growth factor pathway. Ablation of Nr5a1+ cells leads to severe hypospadias, and alters cell differentiation in the penis. This discovery highlights the indispensable role of Nr5a1+ extra-genital cells in urethra closure, shedding light on the biology of penis formation and potential implications for human hypospadias.
2024-12-18 | GSE278744 | GEO
Project description:The lower urinary is derived from the endodermal precursor, the cloaca. Despite common embryological origins, the epithelial linings and surrounding mesenchyme of the bladder and urethra show divergence. The bladder forms from the anterior part of the urogenital sinus, a cloacal derivative formed after septation of the cloaca to give rise to the anorectal and urogenital tracts. The urethra elongates posteriorly and shows sex-specific differences as a result of hormonal action. The bladder is a target for regenerative therapies and tissue reconstruction strategies. A significant shortcoming of these strategies has been the inability to recapitulate all layers of bladder epithelial cells, most importantly the apical uroplakin positive layer that forms a tight, impermeable barrier against components in the urine. The urethral epithelium is contiguous with the bladder epithelium but has distinct cellular architecture and lacks a uroplakin expressing apical layer. We hypothesized that comparison of the developing urethra and bladder epithelium will identify early genes that are responsible for urethra and bladder-specific differentiation. In this study, we compared the epithelial compartments of the developing mouse bladder and urethra to identify genes that are differentially expressed in these two compartments. Our study identified transcription factor genes and other tissue-specific markers that are confined to either the urethra or bladder epithelium. Additionally, we describe sex-specific differences in the lower urinary tract epithelium which are more pronounced between the male and female urethral epithelium and less evident in the bladder epithelium between sexes.
2025-01-01 | GSE253102 | GEO
Project description:The lower urinary is derived from the endodermal precursor, the cloaca. Despite common embryological origins, the epithelial linings and surrounding mesenchyme of the bladder and urethra show divergence. The bladder forms from the anterior part of the urogenital sinus, a cloacal derivative formed after septation of the cloaca to give rise to the anorectal and urogenital tracts. The urethra elongates posteriorly and shows sex-specific differences as a result of hormonal action. The bladder is a target for regenerative therapies and tissue reconstruction strategies. A significant shortcoming of these strategies has been the inability to recapitulate all layers of bladder epithelial cells, most importantly the apical uroplakin positive layer that forms a tight, impermeable barrier against components in the urine. The urethral epithelium is contiguous with the bladder epithelium but has distinct cellular architecture and lacks a uroplakin expressing apical layer. We hypothesized that comparison of the developing urethra and bladder epithelium will identify early genes that are responsible for urethra and bladder-specific differentiation. In this study, we compared the epithelial compartments of the developing mouse bladder and urethra to identify genes that are differentially expressed in these two compartments. Our study identified transcription factor genes and other tissue-specific markers that are confined to either the urethra or bladder epithelium. Additionally, we describe sex-specific differences in the lower urinary tract epithelium which are more pronounced between the male and female urethral epithelium and less evident in the bladder epithelium between sexes.
2025-01-01 | GSE275616 | GEO
Project description:The lower urinary is derived from the endodermal precursor, the cloaca. Despite common embryological origins, the epithelial linings and surrounding mesenchyme of the bladder and urethra show divergence. The bladder forms from the anterior part of the urogenital sinus, a cloacal derivative formed after septation of the cloaca to give rise to the anorectal and urogenital tracts. The urethra elongates posteriorly and shows sex-specific differences as a result of hormonal action. The bladder is a target for regenerative therapies and tissue reconstruction strategies. A significant shortcoming of these strategies has been the inability to recapitulate all layers of bladder epithelial cells, most importantly the apical uroplakin positive layer that forms a tight, impermeable barrier against components in the urine. The urethral epithelium is contiguous with the bladder epithelium but has distinct cellular architecture and lacks a uroplakin expressing apical layer. We hypothesized that comparison of the developing urethra and bladder epithelium will identify early genes that are responsible for urethra and bladder-specific differentiation. In this study, we compared the epithelial compartments of the developing mouse bladder and urethra to identify genes that are differentially expressed in these two compartments. Our study identified transcription factor genes and other tissue-specific markers that are confined to either the urethra or bladder epithelium. Additionally, we describe sex-specific differences in the lower urinary tract epithelium which are more pronounced between the male and female urethral epithelium and less evident in the bladder epithelium between sexes.
2025-01-01 | GSE275615 | GEO
Project description:The lower urinary is derived from the endodermal precursor, the cloaca. Despite common embryological origins, the epithelial linings and surrounding mesenchyme of the bladder and urethra show divergence. The bladder forms from the anterior part of the urogenital sinus, a cloacal derivative formed after septation of the cloaca to form the anorectal and urogenital tracts. The urethra elongates posteriorly and shows sex-specific differences as a result of hormonal action. The bladder is a target for regenerative therapies and tissue reconstruction strategies. A significant shortcoming of these strategies has been the inability to recapitulate all layers of bladder epithelial cells, most importantly the apical uroplakin expressing cell layer that forms a tight, impermeable barrier against components in the urine. Epithelial-mesenchymal interactions are critical for organogenesis. Several studies have shown the ability of embryonic bladder mesenchyme to reprogram non-bladder epithelium to resemble bladder tissue at the molecular and cellular level. In this study, we performed bulk RNA-sequencing on the mesenchymal layers of the developing mouse bladder and urethra and identified compartmentalized organ-specific gene expression. Our study identified transcription factor genes and secreted protein genes specific to the bladder or urethra mesenchymal compartments. Additionally, we describe sex-specific differences in the lower urinary tract mesenchyme which are more pronounced between the male and female urethral mesenchyme and less evident in the bladder mesenchyme between sexes.
2025-01-01 | GSE253103 | GEO
Project description:Circular RNAs (circRNAs) are a unique class of single-stranded RNA molecules with a closed-loop structure that confer enhanced stability, extended protein expression, and resistance to exonucleases, making them promising candidates for RNA therapeutics. In recent years, several methods have been developed to generate circRNAs, including the traditional, scar-containing Anabaena Permuted Intron-Exon (Ana-PIE) method and newer “scarless” circularization approaches. This study introduces a novel scarless circularization method, Split-Coxsackievirus B3-Anabaena Permuted Intron-Exon (Split-CVB3 Ana-PIE, SCAP). Scarless circular RNAs generated using the SCAP system were systematically compared to their scarred counterparts produced by the Ana-PIE system in terms of circularization efficiency, protein expression, stability, and immune response. The SCAP system achieved circularization efficiencies comparable to those of the Ana-PIE system while significantly enhancing protein expression. Scarless circular RNAs exhibited similar stability to scarred circular RNAs and did not trigger significant immune responses. These findings highlight the potential of scarless circular RNAs in gene therapy and vaccine development, demonstrating that removing extraneous sequences improves translation efficiency without compromising stability or immunogenicity. This study provides a foundation for the rational design of circular RNAs, with future efforts focusing on diverse target genes, optimized delivery platforms, and in vivo validation.
2025-03-01 | GSE284757 | GEO
Project description:<p>Urethral microbiome of adolescent males is designed to characterize the microbial communities resident in the urethra of young men, to identify differences in these communities as a function of race/ethnicity, circumcision status, sexual exposures, and uro-genital symptoms. We collect detailed sexual behavior and symptoms data using cellular telephones with Internet access. Specimens are routinely collected at monthly intervals, and intermittently following reported symptoms, specific sexual exposures, or identification of a sexually transmitted infection. We also collect periodic samples from the penile coronal sulcus to better characterize its relationship to the urethral micriobial communities.</p> <p>Participants are ages 14 - 17 at enrollment, and prior history of sexual exposure is not required for participation. Parental permission is obtained for each participant. The planned duration of followup is up to 4 years allowing for prospective observation of both physical and behavioral maturation from middle adolescence into young adulthood.</p> <p>The overall objectives of the project are to better characterize the healthy male urethral microbiome, and to use this information to better understand acquisition of urethritis and sexually transmitted infections, as well as chronic genital pain and prostatitis syndromes that become common among young adults.</p>
| phs000259 | dbGaP
Project description:Acute urethral injuries caused by urethral endoscopy and other mechanical injuries are the main reasons for secondary infection and late urethral stricture. However, there are no studies to explore the transcriptomic changes in urethral injury and the molecular mechanism of urethral injury, which is important for the treatment and cure of urethral injury. Therefore, we used RNA-seq and sRNA-seq profiles from normal and injured urethral tissues to identify and characterize differentially expressed mRNAs and miRNAs. In total, we found 166 differentially expressed mRNAs, of which 69 were upregulated, and 97 were downregulated in injured urethral tissues. The differentially expressed mRNAs were mainly involved in the positive regulation of epithelial cell differentiation, focal adhesion, cell adhesion molecules, protein activation cascade, complement activation, complement and coagulation cascades, and chemokine-mediated signaling pathway. Additionally, we found six upregulated and four downregulated miRNAs, respectively, in the injured urethral tissues. Notably, their target genes were involved in the vascular endothelial growth factor receptor 2 binding, PI3k-Akt signaling pathway, and Notch signaling pathway. In summary, our results suggest that the cell damage response induced by mechanical injury activates the pathological immune response in a variety of ways in injured urethral tissues.
2022-05-31 | GSE182947 | GEO