-
Molecular Biology of the Cell Nov 2017Flow of fluids through the gut, such as milk from a neonatal diet, generates a shear stress on the unilaminar epithelium lining the lumen. We report that exposure to...
Flow of fluids through the gut, such as milk from a neonatal diet, generates a shear stress on the unilaminar epithelium lining the lumen. We report that exposure to physiological levels of fluid shear stress leads to the formation of large vacuoles, containing extracellular contents within polarizing intestinal epithelial cell monolayers. These observations lead to two questions: how can cells lacking primary cilia transduce shear stress, and what molecular pathways support the formation of vacuoles that can exceed 80% of the cell volume? We find that shear forces are sensed by actin-rich microvilli that eventually generate the apical brush border, providing evidence that these structures possess mechanosensing ability. Importantly, we identified the molecular pathway that regulates large vacuole formation downstream from mechanostimulation to involve central components of the autophagy pathway, including ATG5 and LC3, but not Beclin. Together our results establish a novel link between the actin-rich microvilli, the macroscopic transport of fluids across cells, and the noncanonical autophagy pathway in organized epithelial monolayers.
Topics: Actins; Autophagy; Caco-2 Cells; Cell Culture Techniques; Epithelium; Humans; Intestinal Mucosa; Intestines; Microvilli; Stress, Physiological; Vacuoles
PubMed: 28855375
DOI: 10.1091/mbc.E17-01-0021 -
World Journal of Gastroenterology Feb 2003To investigate the possibility of urethral reconstruction with a free colonic mucosa graft and to present our preliminary experience with urethral substitution using a...
AIM
To investigate the possibility of urethral reconstruction with a free colonic mucosa graft and to present our preliminary experience with urethral substitution using a free graft of colonic mucosa for treatment of 7 patients with complex urethral stricture of a long segment.
METHODS
Ten female dogs underwent a procedure in which the urethral mucosa was totally removed and replaced with a free graft of colonic mucosa. A urodynamic study was performed before the operation and sacrifice. The dogs were sacrificed 8 to 16 weeks after the operation for histological examination of urethra. Besides, 7 patients with complex urethral stricture of a long segment were treated by urethroplasty with the use of a colonic mucosal graft. The cases had undergone an average of 3 previous unsuccessful repairs. Urethral reconstruction with a free graft of colonic mucosa ranged from 10 to 17 cm (mean 13.1 cm). Follow-up included urethrography, urethroscopy and uroflowmetry.
RESULTS
Urethral stricture developed in 1 dog. The results of urodynamic studies showed that the difference in the maximum urethral pressure between the pre-operation and pre-sacrifice in the remaining 9 dogs was not of significance (P>0.05). Histological examination revealed that the colonic free mucosa survived inside the urethral lumen of the 10 experimental dogs. Plicae surface and unilaminar cylindric epithelium of the colonic mucosa was observed in dogs sacrificed 8 weeks after the operation. The plicae surface and unilaminar cylindric epithelium of the colonic mucosa was not observed, and metaplastic transitional epithelium covered a large proportion of the urethral mucosa in dogs sacrificed 12 weeks after the operation. Clinically, the patients were followed up for 3-18 months postoperatively (mean 8.5 months). Meatal stenosis was developed in 1 patient 3 months postoperatively and needed reoperation. The patient was voiding very well with urinary peak flow 28.7 ml/s during the follow-up of 9 months after reoperation. The other patients were voiding well with urinary peak flow greater than 15 ml/s. Urethrogram revealed a patent urethra with an adequate lumen with no significant graft sacculation. Neither necrosis of neourethral mucosa nor stenosis at the anastomosis sites has been observed on urethroscopy in 4 patients over 6 months after operation.
CONCLUSION
Urethral mucosa can be replaced by colonic mucosa without damaging the continence mechanism in female dogs. Colonic mucosa graft urethral substitution is a feasible procedure for the treatment of complex urethral stricture of a long segment. The technique may be considered when more conventional options have failed or are contraindicated.
Topics: Adult; Animals; Colon; Dogs; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Surgically-Created Structures; Treatment Outcome; Urethral Stricture; Urologic Surgical Procedures
PubMed: 12532472
DOI: 10.3748/wjg.v9.i2.381 -
Stem Cell Research & Therapy Sep 2021Very small embryonic-like stem cells (VSELs) are a rare population within the ovarian epithelial surface. They contribute to postnatal oogenesis as they have the ability...
Bone marrow-derived mesenchymal stem cells combined with gonadotropin therapy restore postnatal oogenesis of chemo-ablated ovaries in rats via enhancing very small embryonic-like stem cells.
BACKGROUND
Very small embryonic-like stem cells (VSELs) are a rare population within the ovarian epithelial surface. They contribute to postnatal oogenesis as they have the ability to generate immature oocytes and resist the chemotherapy. These cells express markers of pluripotent embryonic and primordial germ cells.
OBJECTIVE
We aimed to explore the capability of VSELs in restoring the postnatal oogenesis of chemo-ablated rat ovaries treated with bone marrow-derived mesenchymal stem cells (BM-MSCs) combined with pregnant mare serum gonadotropin (PMSG).
METHODS
Female albino rats were randomly assigned across five groups: I (control), II (chemo-ablation), III (chemo-ablation + PMSG), IV (chemo-ablation + MSCs), and V (chemo-ablation + PMSG + MSCs). Postnatal oogenesis was assessed through measurement of OCT4, OCT4A, Scp3, Mvh, Nobox, Dazl4, Nanog, Sca-1, FSHr, STRA8, Bax, miR143, and miR376a transcript levels using qRT-PCR. Expression of selected key proteins were established as further confirmation of transcript expression changes. Histopathological examination and ovarian hormonal assessment were determined.
RESULTS
Group V displayed significant upregulation of all measured genes when compared with group II, III or IV. Protein expression confirmed the changes in transcript levels as group V displayed the highest average density in all targeted proteins. These results were confirmed histologically by the presence of cuboidal germinal epithelium, numerous primordial, unilaminar, and mature Graafian follicles in group V.
CONCLUSION
VSELs can restore the postnatal oogenesis in chemo-ablated ovaries treated by BM-MSCs combined with PMSG.
Topics: Animals; Bone Marrow; Embryonic Stem Cells; Female; Gonadotropins; Mesenchymal Stem Cells; Oogenesis; Ovary; Rats
PubMed: 34579781
DOI: 10.1186/s13287-021-02415-5