Biology subjects

Cadena, M.

Publications and source records attributed to Cadena, M..

3 recordsLinked to original sources

bioRxiv2021

OSTEOPONTIN DEFICIENCY LEADS TO THE RESOLUTION OF PROSTATIC FIBROSIS AND INFLAMMATION

Fibrogenic and inflammatory processes in the prostate are linked to the development of lower urinary tract symptoms (LUTS) in men. Our previous studies identified that osteopontin (OPN), a pro-fibrotic cytokine, is abundant in the prostate of men with LUTS and its secretion is stimulated by inflammatory cytokines potentially to drive fibrosis. This study investigates whether the lack of OPN ameliorates inflammation and fibrosis in the mouse prostate. We instilled uropathogenic E. coli (UTI89) or saline (control) transurethrally to C57BL/6J (WT) or Spp1tm1Blh/J (OPN-KO) mice and collected the prostates one or 8 weeks later. We found that OPN mRNA and protein expression were significantly induced by E. coli-instillation in the dorsal prostate (DP) after one week in WT mice. Deficiency in OPN expression led to decreased inflammation and fibrosis and the prevention of urinary dysfunction after 8 weeks. RNAseq analysis identified that E. coli-instilled WT mice expressed increased levels of inflammatory and fibrotic marker RNAs compared to OPN-KO mice including Col3a1, Dpt, Lum and Mmp3 which were confirmed by RNAscope. Our results indicate that OPN is induced by inflammation and prolongs the inflammatory state; genetic blockade of OPN accelerates recovery after inflammation, including a resolution of prostate fibrosis.

pathology↗

bioRxiv2020

A Uropathogenic E. coli UTI89 model of prostatic inflammation and collagen accumulation for use in studying aberrant collagen production in the prostate

Bacterial infection is one known etiology of prostatic inflammation. Prostatic inflammation is associated with prostatic collagen accumulation and both are linked to progressive lower urinary tract symptoms in men. We characterized a model of prostatic inflammation utilizing transurethral instillations of E. coli UTI89 in C57BL/6J male mice with the goal of determining the optimal instillation conditions, understanding the impact of instillation conditions on urinary physiology, and identifying ideal prostatic lobes and collagen 1a1 prostatic cell types for further analysis. The smallest instillation volume tested (50 {micro}L) distributes exclusively to bladder, 100 and 200 {micro}L volumes distributes to bladder and prostate, and a 500 {micro}L volume distributes to bladder, prostate and ureter. A threshold optical density (OD) of 0.4 E. coli UTI89 in the instillation fluid is necessary for significant (p < 0.05) prostate colonization. E. coli UTI89 infection results in a low frequency, high volume spontaneous voiding pattern. This phenotype is due to exposure to E. coli UTI89, not catheterization alone, and is minimally altered by a 50 {micro}L increase in instillation volume and doubling of E. coli concentration. Prostate inflammation is isolated to the dorsal prostate and is accompanied by increased collagen density. This is partnered with increased density of PTPRC+, ProCOL1A1+ co-positive cells and decreased density of ACTA2+, ProCOL1A1+ co-positive cells. Overall, we determined that this model is effective in altering urinary phenotype and producing prostatic inflammation and collagen accumulation in mice.

physiology↗

bioRxiv2019

Systemic Brain Tumor Delivery of Synthetic Protein Nanoparticles for Glioblastoma Therapy

Glioblastoma multiforme (GBM), the most aggressive form of brain cancer, has witnessed very little clinical progress over the last decades, in parts, due to the absence of effective drug delivery strategies. Intravenous injection is the least invasive delivery route to the brain, but has been severely limited by the blood-brain barrier (BBB). Inspired by the capacity of natural proteins and viral particulates to cross the BBB, we engineered a synthetic protein nanoparticle (SPNP) based on polymerized human serum albumin (HSA) equipped with the cell-penetrating peptide iRGD. SPNPs containing siRNA against Signal Transducer and Activation of Transcription 3 factor (STAT3i) result in in vitro and in vivo downregulation of STAT3, a central hub associated with GBM progression. When combined with the standard of care, ionized radiation, STAT3i SPNPs result in tumor regression and long-term survival in 87.5% of GBM bearing mice and primes the immune system to develop anti-GBM immunological memory.

bioengineering↗