The Role of Extracellular Matrix Proteins in the Urinary Tract: A Literature Review (original) (raw)
Related papers
The bladder extracellular matrix. Part I: architecture, development and disease
Nature Reviews Urology, 2009
| From the earliest studies with epithelial cells implanted into detrusor muscle to later experiments on smooth muscle in defined collagen gels, cell niche and extracellular matrix (ECM) have been clearly shown to orchestrate cellular behavior and fate whether quiescent, migratory, or proliferative. Normal matrix can revert transformed cells to quiescence, and damaged matrix can trigger malignancy or dedifferentiation. ECM influence in disease, development, healing and regeneration has been demonstrated in many other fields of study, but a thorough examination of the roles of ECM in bladder cell activity has not yet been undertaken. Structural ECM proteins, in concert with adhesive proteins, provide crucial structural support to the bladder. Both structural and nonstructural components of the bladder have major effects on smooth muscle function, through effects on matrix rigidity and signaling through ECM receptors. While many ECM components and receptors identified in the bladder have specific known functions in the vascular smooth musculature, their function in the bladder is often less well defined. In cancer and obstructive disease, the ECM has a critical role in pathogenesis. The challenge in these settings will be to find therapies that prevent hyperproliferation and encourage proper differentiation, through an understanding of matrix effects on cell biology and susceptibility to therapeutics.
Journal of Pediatric Urology, 2010
To investigate histopathological changes in ureteropelvic junction obstruction (UPJO) from an etiological perspective. Medical records of patients with UPJO were reviewed and pathological specimens collected. Nephrectomy materials from forensic autopsies were taken as controls. Specimens were assessed with light microscopy. Fibronectin, type 4 collagen, laminin, Bax and Bcl-2 expression for apoptosis, together with interstitial cells of Cajal determination with c-kit were determined immunohistochemically. Staining scores were evaluated semiquantitatively. Results were evaluated using Mann-Whitney U-test. Control group comprised 14 children (median age, 3.5 years; 6 months-17 years). Study group comprised 22 children with UPJO (median age, 9 months; 1 month-10 years). Light microscopy revealed non-specific inflammation, epithelial proliferation and atrophy with fibrosis in the smooth muscle of the UPJ in all patients. Fibronectin, type 4 collagen and laminin were found to be significantly increased in UPJO at the intrafascicular space of smooth muscle and the matrix of stroma. Bcl-2 expression was increased in UPJO. c-Kit was unable to stain interstitial cells of Cajal, but staining for mast cells was significant. High expression of fibronectin, laminin and type 4 collagen may indicate a relation to the pathogenesis of UPJO. Defective kidney morphogenesis, during branching and tubulogenesis of ureteric bud, may be responsible for this congenital pathology.
Rapid degradation of extracellular matrix proteins by normal human uroepithelial cells
Cancer research, 1990
The degradation of subendothelial and smooth muscle matrices by normal and neoplastic uroepithelial cells grown under serum-free conditions was examined. Normal urothelial cells were compared with neoplastic cells derived from a low grade papillary tumor (RT4) and a more invasive carcinoma (EJ). Low levels of degradation were observed with all cell types in serum-free medium alone. Supplementing the medium with plasminogen increased the degradative activity of each cell type. Logarithmically growing normal urothelial cells degraded extracellular matrix proteins 6 to 14 times faster on a per cell basis than their transformed counterparts. Analysis of the residual matrix constituents revealed that, while the levels of glycoprotein breakdown by the normal and neoplastic cells were similar, the normal cells degraded more of the collagen components than the neoplastic cells. Epidermal growth factor and cell density were examined as possible regulators of degradative activity. The neoplas...
Imbalance in extracellular matrix degradation in urethral stricture
Research and Reports in Urology, 2018
Background: Extracellular matrix degradation may play an important role in the etiology of urethral stricture. MMP1 and TIMP1 are involved in extracellular matrix degradation. The aim of this study was to investigate the roles of MMP1, TIMP1, and MMP1:TIMP1 ratio at the remodeling phase of urethral stricture in an animal model. Methods: This research was carried out in collaboration between the Bogor Institute of Agriculture, Universitas Indonesia, and the Eijkman Institute Indonesia. This was an experimental in vivo study in adult male New Zealand rabbits, divided into two groups: a urethral stricture group and a control group. Euthanasia was performed in four rabbits of each group on days 7, 14, 21, 28, and 56. Urethral stricture was confirmed with an 8 F urethral catheter. Several laboratory examinations were done, including H&E and Masson trichrome staining, immunohistochemistry, and ELISA, to determine levels of MMP1 and TIMP1. Percentages of total collagen and collagen type 1 were counted with ImageJ 1.46q software. A general linear model was used for statistic analysis. Results: We found that the level of MMP1 was lower, TIMP1 higher, and MMP1:TIMP1 ratio lower in the urethral stricture group than the control group. There was a correlation between MMP1 level with total collagen percentage (r=0.561, P=0.010) and no correlation between TIMP1 and total collagen (r=0.307, P=0.188). Conclusion: Imbalance in extracellular matrix degradation was marked by decreased MMP1 level and MMP1:TIMP1 ratio and increased TIMP1 level. This results showed that urethral stricture is not only caused by collagen decomposition, but also by the imbalance of extracellular matrix degradation.
EXTRACELLULAR MATRIX DEGRADATION AND REDUCED NERVE SUPPLY IN REFLUXING URETERAL ENDINGS
Journal of Urology, 2004
To investigate the extracellular matrix microenvironment and nerve supply of ureteropelvic junctions (UPJs) in children with intrinsic UPJ obstruction. Congenital UPJ obstruction is the most common cause of neonatal hydronephrosis. Although many studies investigating the molecular changes within this segment have been performed, the underlying mechanisms of UPJ obstruction are still unclear.
BJU International, 2005
cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. RESULTS Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. CONCLUSION Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression. KEYWORDS tenascin, fibronectin, collagen type IV, laminin, bladder cancer OBJECTIVE To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. MATERIALS AND METHODS Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27-89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating
Role of extracellular matrix components and structure in new renal models in vitro
Frontiers in Physiology
The extracellular matrix (ECM), a complex set of fibrillar proteins and proteoglycans, supports the renal parenchyma and provides biomechanical and biochemical cues critical for spatial-temporal patterning of cell development and acquisition of specialized functions. As in vitro models progress towards biomimicry, more attention is paid to reproducing ECM-mediated stimuli. ECM’s role in in vitro models of renal function and disease used to investigate kidney injury and regeneration is discussed. Availability, affordability, and lot-to-lot consistency are the main factors determining the selection of materials to recreate ECM in vitro. While simpler components can be synthesized in vitro, others must be isolated from animal or human tissues, either as single isolated components or as complex mixtures, such as Matrigel or decellularized formulations. Synthetic polymeric materials with dynamic and instructive capacities are also being explored for cell mechanical support to overcome th...
Extracellular Matrix Changes in Urethral Stricture Disease
The Journal of Urology, 2002
Purpose: Glycosaminoglycans (GAGs) and collagen are major components of the extracellular matrix and they have key roles in fibrotic diseases. Little is known about the molecular environment in urethral stricture and the majority of the studies available focused on collagen analysis. However, to our knowledge there are no data on GAG composition in urethral stricture disease.
Histology and histopathology, 2014
Benign prostatic hyperplasia (BPH) nodules increase urethral resistance, resulting in "pressure" of tissue expansion to the urethra and leads to an increase in outflow resistance, accompanied by characteristic lengthening of the prostatic urethra. The goal of this investigation was to analyze and quantify changes of the histological components in the prostatic urethra of patients with BPH and compare with a control group. Prostatic urethra tissue samples were obtained from ten patients (age range 63 to 79 years, mean 66) with clinical symptoms of bladder outlet obstruction who had undergone open prostatectomy. The ten control group samples (urethral tissue samples from the transitional zone) were collected from prostates obtained during autopsy of accidental death adults of less than 25 years. The Volumetric density (Vv) of the histological components was determined with stereological methods from 25 random fields per sample using the point-count method with a M-42 grid te...