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Osteopontin Deficiency Ameliorates Prostatic Fibrosis and Inflammation
- Source :
- International Journal of Molecular Sciences, Vol 22, Iss 12461, p 12461 (2021), International Journal of Molecular Sciences, Volume 22, Issue 22
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- 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<br />genetic blockade of OPN accelerates recovery after inflammation, including a resolution of prostate fibrosis.
- Subjects :
- Male
Lumican
MMP3
chronic inflammation
medicine.medical_treatment
Mice
Fibrosis
Prostate
Uropathogenic Escherichia coli
Osteopontin
lower urinary tract symptoms
Biology (General)
Escherichia coli Infections
Spectroscopy
Mice, Knockout
Extracellular Matrix Proteins
biology
General Medicine
Computer Science Applications
Chemistry
medicine.anatomical_structure
Cytokine
Urinary Tract Infections
Matrix Metalloproteinase 3
medicine.symptom
Signal Transduction
medicine.medical_specialty
QH301-705.5
extracellular matrix
Inflammation
prostatic fibrosis
Article
Catalysis
Proinflammatory cytokine
Inorganic Chemistry
stomatognathic system
Lower urinary tract symptoms
Internal medicine
medicine
Animals
Humans
RNA, Messenger
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
benign prostatic hyperplasia
business.industry
Organic Chemistry
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
Collagen Type III
Endocrinology
Chondroitin Sulfate Proteoglycans
Gene Expression Regulation
biology.protein
business
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 22
- Issue :
- 12461
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....3be36c69dc29a81c5f7ad9d4977bd1d0