scholarly journals Spatiotemporal Expression of SHH/GLI Signaling in Human Fetal Bladder Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Haibao Zhang ◽  
Shan Xu ◽  
Dalin He ◽  
Xinyang Wang ◽  
Guodong Zhu
Keyword(s):  
Smooth Muscle ◽  
Signaling Pathway ◽  
Expression Patterns ◽  
Muscle Layer ◽  
Nuclear Antigen ◽  
Human Fetuses ◽  
Cell Nuclei ◽  
Human Bladder ◽  
Shh Signaling ◽  
Signaling Components

Objectives: Sonic hedgehog (SHH) signaling is important in bladder development. Mice with defective hedgehog signaling develop bladder anomalies. Clinically, urinary tract malformations are reported in human fetuses and infants with mutations of SHH and related signaling pathway genes. Information on the expression of SHH and associated signaling genes in normal human bladder development is fragmentary. This study determined the temporal and spatial expression patterns of SHH signaling pathway components in human fetal bladders by immunohistochemistry (IHC).Material and Methods: Twenty-four bladder specimens from 16 male and 8 female human fetuses aged 12- to 36-week (wk) were obtained from the First Affiliated Hospital of Xi'an Jiaotong University. The tissue slides were processed for IHC staining with SHH, Patched1 (PTC-1), Patched2 (PTC-2), Smoothened (SMO), GLI1 and proliferating cell nuclear antigen (PCNA). The expression levels of each gene were analyzed by semi-quantitative histological scoring system.Results: High intensity of SHH and SMO expression was detected in developing bladder urothelial cells, with no staining in lamina propria (LP), but with minimal expression of SMO in differentiating smooth muscle (SM) layers. The spatial distribution pattern of PTC1 and GLI1 was more complex with minimal expression in the LP layer, moderate expression in the SM layer, and high expression in the urothelium. PTC2 expression was mainly localized in the urothelium and LP, but no expression in the SM layer. All of the SHH signaling components were detected in fetal bladder tissues throughout the development, with expression peaks at 12- and 23-wk, coinciding with high cell proliferation as indicated by PCNA staining in the cell nuclei of urothelium and SM.Conclusions: The autocrine SHH signaling in the developing urothelium, and paracrine SHH signaling in the developing smooth muscle layer, mediated by SMO, PTC-1 and GLI1 were demonstrated during human bladder development. Expression of SHH signaling components peaked at 12-and 23-wk. The first expression peak at 12-wk may relate to urothelium growth, SM induction, and dilation of the bladder cavity. The second expression peaked at 23-wk may relate to urothelium and SM layer differentiation.

M 3 receptor modulates extracellular matrix synthesis via ERK1/2 signaling pathway in human bladder smooth muscle cells

2020 ◽  
Vol 121 (11) ◽  
pp. 4496-4504
Author(s):  
Shulian Chen ◽  
Banghua Liao ◽  
Xi Jin ◽  
Tangqiang Wei ◽  
Qing He ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Muscle Cells ◽  
Bladder Smooth Muscle ◽  
Matrix Synthesis ◽  
Human Bladder

scholarly journals MicroRNA 4323 induces human bladder smooth muscle cell proliferation under cyclic hydrodynamic pressure by activation of erk1/2 signaling pathway

2016 ◽  
Vol 242 (2) ◽  
pp. 169-176 ◽  
Author(s):  
Yi Sun ◽  
Deyi Luo ◽  
Yuchun Zhu ◽  
Kunjie Wang
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Signaling Pathway ◽  
Hydrodynamic Pressure ◽  
Proliferation Index ◽  
Bladder Smooth Muscle ◽  
Human Bladder ◽  
Qrt Pcr ◽  
Lyn Kinase ◽  
Bladder Smooth Muscle Cell

We cultivated human bladder smooth muscle cells (HBSMCs) under pressures of 0 or 200 cm H2O pressure for 24 h, before using microarray technology to extract and analyze the different expressions of miRNAs and mRNAs in the two groups. We also predicted the target mRNA of the miDNA and performed functional forecasting. Changes in miRNA were identified by quantitative real-time polymerase chain reaction (qRT-PCR) after overexpressing miRNA by transfection. We used flow cytometry to examine HBSMC proliferation, and we used qRT-PCR and Western blot analyses to quantify the expression and activation of mRNAs and proteins. There were nine upregulated and four downregulated miRNAs involved in cell proliferation, including miR 4323, which was identified by qRT-PCR ( p = 0.027). In addition, miR 4323 was shown to inhibit LYN ( p = 0.031), decrease lyn kinase ( p = 0.037), and promotes the phosphorylation of extracellular regulated protein kinases 1 and 2 (Erk1/2) ( p = 0.004). Moreover, overexpression of miR 4323 activated the proliferation pathway regulated by Erk1/2. Then, miR 4323 was shown to stimulate the proliferation of HBSMCs, with the proliferation index improving from 30.84 ± 4.57 to 52.13 ± 3.41 ( p = 0.001). In summary, when the miRNA miR 4323 was overexpressed under cyclic hydrodynamic pressure, LYN is decreased and the Erk1/2 signaling pathway is activated; in addition, miR 4323 is involved in HBSMC proliferation when under hydrodynamic pressure.

Sonic Hedgehog Signaling is Important in Tooth Root Development

2006 ◽  
Vol 85 (5) ◽  
pp. 427-431 ◽  
Author(s):  
M. Nakatomi ◽  
I. Morita ◽  
K. Eto ◽  
M.S. Ota
Keyword(s):  
Sonic Hedgehog ◽  
Root Development ◽  
Mutant Cell ◽  
Expression Patterns ◽  
Nuclear Antigen ◽  
Tooth Root ◽  
Shh Signaling ◽  
Hertwig’S Epithelial Root Sheath ◽  
Root Sheath

Hertwig’s epithelial root sheath (HERS) is important for tooth root formation, but the molecular basis for the signaling of root development remains uncertain. We hypothesized that Sonic hedgehog (Shh) signaling is involved in the HERS function, because it mediates epithelial-mesenchymal interactions during embryonic odontogenesis. We examined the gene expression patterns of Shh signaling in murine developing molar roots. Shh and Patched2 transcripts were identified in the HERS, whereas Patched1, Smoothened, and Gli1 were expressed in the proliferative dental mesenchyme in addition to the HERS. To confirm whether Shh signaling physiologically functions in vivo, we analyzed mesenchymal dysplasia ( mes) mice carrying an abnormal C-terminus of the PATCHED1 protein. In the mutant, cell proliferation was repressed around the HERS at 1 wk. Moreover, the molar eruption was disturbed, and all roots were shorter than those in control littermates at 4 wks. These results indicate that Shh signaling is important in tooth root development. Abbreviations used: BrdU, 5-bromo-2′-deoxyuridine; HERS, Hertwig’s epithelial root sheath; NFI-C/CTF, nuclear factor Ic/CAAT box transcription factor; PCNA, proliferating cell nuclear antigen; Ptc, patched; Shh, sonic hedgehog; Smo, smoothened.

Studies on binding sites, contents, and effects of AVP in isolated bladder and urethra from rabbits and humans

1991 ◽  
Vol 261 (4) ◽  
pp. R865-R874 ◽  
Author(s):  
F. Holmquist ◽  
S. Lundin ◽  
B. Larsson ◽  
H. Hedlund ◽  
K. E. Andersson
Keyword(s):  
Smooth Muscle ◽  
Binding Sites ◽  
Membrane Binding ◽  
Electrical Field Stimulation ◽  
Muscle Layer ◽  
Binding Studies ◽  
Human Bladder ◽  
Circular Smooth Muscle ◽  
Rabbit Bladder ◽  
Displacement Experiments

The binding sites, contents, and effects of arginine vasopressin (AVP) were studied in isolated bladder and urethral preparations from rabbits and humans. In all tissues, higher levels of AVP-like immunoreactivity (AVP-LI) were detected than those normally found in plasma. Radioligand membrane binding studies using [3H]AVP as the ligand revealed the existence of a single population of binding sites in the rabbit bladder, and displacement experiments indicated that the receptor was of the V1 subtype. By autoradiography, [3H]AVP binding sites in the rabbit bladder were shown to be located on both circularly and longitudinally oriented smooth muscle cells, as well as in the submucosa at the part adjacent to the urothelium. In the rabbit urethra, the binding sites were confined mainly to the circular smooth muscle layer. Neither radioligand membrane binding studies nor autoradiography revealed any specific [3H]AVP binding sites in the human bladder. AVP contracted rabbit bladder and urethral preparations concentration dependently. The contractions were inhibited by the V1-receptor selective antagonist A16 in a noncompetitive manner. However, A16 had no effects on contractions elicited by electrical-field stimulation. In preparations of the human bladder and urethra, AVP in concentrations up to 10(-5) M did not have any contractile effects. These results suggest that in the rabbit and human lower urinary tract, AVP-LI is synthesized locally and/or extracted from the circulation. It is unlikely that AVP is directly involved in the neurotransmission in these tissues, although in the rabbit bladder and urethra a modulatory role cannot be excluded.

Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate

Life Sciences ◽  
2021 ◽  
Vol 271 ◽  
pp. 119198
Author(s):  
Luana Araújo Manso ◽  
Barbara Costa Malmann Medeiros ◽  
Giovanna Amaral Rodrigues ◽  
Jordana Gomes Ramos ◽  
Mara Rúbia Marques ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Layer ◽  
Nuclear Morphology ◽  
Smooth Muscle Layer

scholarly journals Influence of layer separation on the determination of stomach smooth muscle properties

2021 ◽  
Author(s):  
Mischa Borsdorf ◽  
Markus Böl ◽  
Tobias Siebert
Keyword(s):  
Smooth Muscle ◽  
Muscle Fibers ◽  
Smooth Muscles ◽  
Muscle Layer ◽  
Uniaxial Tensile ◽  
Muscle Properties ◽  
Layer Separation ◽  
Isotonic Contractions ◽  
Longitudinal Layer

AbstractUniaxial tensile experiments are a standard method to determine the contractile properties of smooth muscles. Smooth muscle strips from organs of the urogenital and gastrointestinal tract contain multiple muscle layers with different muscle fiber orientations, which are frequently not separated for the experiments. During strip activation, these muscle fibers contract in deviant orientations from the force-measuring axis, affecting the biomechanical characteristics of the tissue strips. This study aimed to investigate the influence of muscle layer separation on the determination of smooth muscle properties. Smooth muscle strips, consisting of longitudinal and circumferential muscle layers (whole-muscle strips [WMS]), and smooth muscle strips, consisting of only the circumferential muscle layer (separated layer strips [SLS]), have been prepared from the fundus of the porcine stomach. Strips were mounted with muscle fibers of the circumferential layer inline with the force-measuring axis of the uniaxial testing setup. The force–length (FLR) and force–velocity relationships (FVR) were determined through a series of isometric and isotonic contractions, respectively. Muscle layer separation revealed no changes in the FLR. However, the SLS exhibited a higher maximal shortening velocity and a lower curvature factor than WMS. During WMS activation, the transversally oriented muscle fibers of the longitudinal layer shortened, resulting in a narrowing of this layer. Expecting volume constancy of muscle tissue, this narrowing leads to a lengthening of the longitudinal layer, which counteracted the shortening of the circumferential layer during isotonic contractions. Consequently, the shortening velocities of the WMS were decreased significantly. This effect was stronger at high shortening velocities.

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