Dataset Information

Development and Characterization of an Inducible Tensin1 Deficient Transgenic Murine Model

ABSTRACT: Tensin1 (TNS1) is a key component of focal and fibrillar adhesions, mediating fibrillogenesis, as well as the transduction of mechanical cues and adhesive signaling. To enable further TNS1 characterization, we have developed a novel transgenic mouse that allows for temporally controlled and lineage specific knockout of TNS1. We found no differentially observed effects of TNS1 knockout on mouse health, breeding capacity, or vital organ histopathology. In contrast, RNA sequencing analysis identified 171 differentially expressed genes with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrating differential expression in osteoclast differentiation and a number of pathways involved in host immune response. Furthermore, STRING pathway analysis showed differential regulation of genes involved in B-cell and myeloid-related signaling pathways, a number of which were validated by reverse transcription-quantitative polymerase chain reaction (RT qPCR). These findings were corroborated by impaired function of TNS1 siRNA monocytes and increased detection of lymphocytes in the bronchoalveolar lavage within days following TNS1 knockout. This study provides a novel understanding of the phenotypic and genotypic changes that occur following knockout of TNS1 that may lead to subsequent understanding of its role in disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE319060 | GEO | 2026/02/14

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Post-operative abdominal adhesions are the leading cause of bowel obstruction and a major cause of chronic pain and infertility. Further, adhesion formation complicates any re-operative strategy, increasing the length of surgery and rendering a safe minimally invasive approach impossible. Despite the prevalence of abdominal adhesions, which form following 50-90% of abdominal operations, no proven preventative or treatment strategy has been developed. Our group previously established a mouse model to study adhesive disease in vivo and explored adhesion biology across mouse and human tissues. We established that adhesions derive primarily from the visceral peritoneum, are composed of poly-clonally proliferating tissue-resident fibroblasts, and identified that modulation of JUN signaling regulates abdominal adhesiogenesis following surgery. We identified a small molecule JUN inhibitor (T-5224) that decreases adhesion formation. Here, we encapsulated T-5224 in a shear-thinning hydrogel with anti-adhesion properties for intra-peritoneal delivery and sustained-release for post-operative adhesion prevention. We extensively characterized this novel therapeutic system, and found it to be safe, systemically well-tolerated, and efficacious in reducing adhesions in our mouse model. Furthermore, this therapeutic system minimizes not only the quantity of adhesions that form, but also limits the maturation of adhesion fibrosis at an ultrastructural level. Critical towards clinical translation, we developed a large mammal (porcine) preclinical model of adhesions with bowel resection and showed that the T-5224-hydrogel therapeutic provides robust adhesion prevention without deleterious effects on bowel anastomosis or abdominal wall (laparotomy) wound healing. At a single-cell transcriptomic level, treated fibroblasts in our pig model show decreased JUN and associated pathway signaling. Adhesion biology shares close similarities across surgical sites (e.g. thoracic, joint space, neurological); as such, this formulation has significant potential for applicability across the body. Material properties of the T-5224-hydrogel formulation, such as shear-thinning and self-healing, also facilitate ease of open or minimally invasive application. Therefore, these results are promising for immediate and high-impact translation to patient care to address a common, unmet clinical need.

Dataset Information

Development and Characterization of an Inducible Tensin1 Deficient Transgenic Murine Model

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets