scholarly journals Seasonal expressions of VEGF and its receptors VEGFR1 and VEGFR2 in the prostate of the wild ground squirrels (Spermophilus dauricus)

2021 ◽  
Vol 65 (2) ◽  
Author(s):  
Yuchen Yao ◽  
Wenqian Xie ◽  
Di Chen ◽  
Yingying Han ◽  
Zhengrong Yuan ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Breeding Season ◽  
Stromal Cells ◽  
Seasonal Changes ◽  
Ground Squirrels ◽  
Vascular Endothelial ◽  
Expression Levels ◽  
Breeding Seasons ◽  
Endothelial Growth Factor ◽  
Endothelial Growth Factors

As a vital male accessory reproductive gonad, the prostate requires vascular endothelial growth factors for promoting its growth and development. In this study, we investigated the localizations and expressions of vascular endothelial growth factor (VEGF) and its receptors including VEGF-receptor1 (VEFGR1) and VEGF-receptor2 (VEGFR2) in the prostate of the wild ground squirrels during the breeding and the non-breeding seasons. The values of total prostate weight and volume in the breeding season were higher than those in the non-breeding season. Histological observations showed that the exocrine lumens of the prostate expanded in the breeding season and contracted in the non-breeding season. The mRNA expression levels of VEGF and VEGFR2 in the prostate were higher in the breeding season than those in the non-breeding season, but the mRNA expression level of VEGFR1 had no significant change between the breeding and non-breeding seasons. Immunohistochemical results revealed that VEGF, VEGFR1 and VEGFR2 were presented in epithelial and stromal cells during the breeding and non-breeding seasons. In addition, the microvessels of the prostate were widely distributed and the number of microvessels increased obviously in the breeding season, while decreased sharply in the non-breeding season. These results suggested that expression levels of VEGF and VEGFR2 might be correlated with seasonal changes in morphology and functions of the prostate, and VEGF might serve as pivotal regulators to affect seasonal changes in the prostate functions of the wild male ground squirrels via an autocrine/paracrine pathway.

scholarly journals Seasonal expressions of androgen receptor, estrogen receptors and cytochrome P450 aromatase in the uteri of the wild Daurian ground squirrels (Spermophilus dauricus)

2018 ◽  
Author(s):  
Yu Wang ◽  
Ziyi Wang ◽  
Wenyang Yu ◽  
Xia Sheng ◽  
Haolin Zhang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Androgen Receptor ◽  
Breeding Season ◽  
Stromal Cells ◽  
Seasonal Changes ◽  
Ground Squirrels ◽  
Sex Steroid ◽  
Expression Levels ◽  
Cytochrome P450 Aromatase ◽  
Glandular Cells

The reproductive tissues including the uterus undergo dramatic changes in seasonal breeders from the breeding to non-breeding seasons. Classically, sex steroid hormones play important roles in the uterine morphology and functions. To clarify the relationship between sex steroid hormones and seasonal changes in the uterine morphology and functions, the wild Daurian ground squirrels (Spermophilus dauricus) were used as seasonal breeder model. And the immunolocalizations and expression levels of androgen receptor (AR), estrogen receptors α and β (ERα and ERβ) and cytochrome P450 aromatase (P450arom) were investigated in the uteri of the wild Daurian ground squirrels in the breeding (April) and the non-breeding (June) seasons via immunohistochemistry, Western blot and RT-PCR. Histologically, the uterine weight, the thickness of endometrium and the glandular density were significantly higher in the uteri of the breeding season than those of the non-breeding season. In both seasons, the immunostaining of AR was only presented in stromal cells of the uteri; the positive staining of ERα and ERβ were localized in stromal cells and glandular cells; P450arom was merely immunolocalized in glandular cells. The protein and mRNA expression levels of ERα, ERβ and P450arom were higher in the uteri of the breeding season than those of the non-breeding season; conversely, the expressions of AR were higher in the uteri of the non-breeding season comparing with those of the breeding season in both protein and mRNA levels. The AR: ER ratio in the uteri of the non-breeding season exceeded the AR: ER ratio in the uteri of the breeding season in the wild Daurian ground squirrels. These results suggested that seasonal changes in the expression levels of AR, ERs and P450arom might be correlated with the uterine morphology and histology changes, and estrogen may play an important autocrine/paracrine role in regulating the uterine functions of the wild Daurian ground squirrels.

scholarly journals Rapamycin as a potent and selective inhibitor of vascular endothelial growth factor receptor in breast carcinoma

2020 ◽  
Author(s):  
Muhammad Shahidan Muhammad Sakri ◽  
Wan Faiziah Wan Abdul Rahman ◽  
Tengku Ahmad Damitri Al-Astani Tengku Din ◽  
Hasnan Jaafar ◽  
Vinod Gopalan
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Breast Carcinoma ◽  
Mrna Expression ◽  
Platelet Factor 4 ◽  
Vascular Endothelial ◽  
Platelet Factor ◽  
Expression Levels ◽  
Endothelial Growth Factor ◽  
Mrna Expression Levels

AbstractAngiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1, and Flt-4, have been found to play an essential role in regulating angiogenesis. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4, and rapamycin+platelet factor-4. The tumors were subsequently subjected to immunohistological protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semi-quantitative scoring method, while the mRNA expression levels were analyzed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4 treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent anti-angiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.

Seasonal changes of mitochondrial autophagy and oxidative response in the testis of the wild ground squirrels (Spermophilus dauricus)

2021 ◽  
Author(s):  
Yuhan Wang ◽  
Ruting Su ◽  
Pinxuan Liu ◽  
Zhengrong Yuan ◽  
Yingying Han ◽  
...  
Keyword(s):  
Breeding Season ◽  
Seasonal Changes ◽  
Sperm Count ◽  
Cell Types ◽  
Redox Balance ◽  
Ground Squirrels ◽  
Therapeutic Interventions ◽  
Mitochondrial Regulation ◽  
In The Wild ◽  
Breeding Seasons

Mitochondria are the main organelles for mammalian energy metabolism and have been implicated in the regulation of germ cell maintenance and spermatogenesis. However, little is known about the changes in the mitochondria of the testis of seasonal breeders. Here, we characterized the seasonal changes in the mitochondria in the testis of the wild ground squirrels. Increased testicle weight, seminiferous tubule diameter and sperm count were observed in the wild ground squirrels at the breeding season. RNA-seq analysis of the wild ground squirrel testes revealed that mitochondrial-related genes were expressed differentially between the breeding and non-breeding seasons. Immunohistochemical staining showed that key mitophagy factors including PINK1, MFN2, and PARKIN were highly expressed in various cell types of testis during the breeding season. In addition, the abundance and enzymatic activities of mitochondrial-localized antioxidative enzymes SOD2 (Superoxide dismutase 2) and Catalase were decreased in the testis during the breeding season, suggesting a tightly controlled redox balance at least partially facilitated by mitophagy during the seasonal breeding. Taken together, our study reveals that mitochondrial autophagy and oxidative stress may be implicated in the seasonal reproductive recrudescence of the wild ground squirrels, which deepens our understanding of the mitochondrial regulation of seasonal reproductivity in wildlife and provides new insights into the development of potential therapeutic interventions of male infertility.

scholarly journals Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model

2021 ◽  
Vol 22 (2) ◽  
pp. 931
Author(s):  
Jihyun Lee ◽  
Yujin Jung ◽  
Seo won Jeong ◽  
Ga Hee Jeong ◽  
Gue Tae Moon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Normal Skin ◽  
Skin Lesions ◽  
Hippo Signaling ◽  
Vascular Endothelial ◽  
Expression Levels ◽  
Hippo Signaling Pathway ◽  
Endothelial Growth Factor

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.

scholarly journals Vascular endothelial growth factor 165 inhibits pro-fibrotic differentiation of stromal cells via the DLL4/Notch4/smad7 pathway

2019 ◽  
Vol 10 (9) ◽  
Author(s):  
Haining Lv ◽  
Ziqing Nan ◽  
Peipei Jiang ◽  
Zhiyin Wang ◽  
Minmin Song ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Pathological Feature ◽  
Vascular Endothelial ◽  
Endometrial Stromal Cells ◽  
Asherman’S Syndrome ◽  
Menstrual Cycles ◽  
Human Control ◽  
Endothelial Growth Factor ◽  
Targeting Strategy ◽  
Uterine Infertility

Abstract Endometrial fibrosis is the main pathological feature of Asherman’s syndrome (AS), which is the leading cause of uterine infertility. Much is known about the expression of VEGF165 in luminal/glandular epithelial cells and stromal cells of the endometrium in normal menstrual cycles; however, less is known about the role and mechanism of VEGF165 in endometrial fibrosis. Herein, we report that VEGF165 is a key regulator in endometrial stromal cells to inhibit α-SMA and collagen 1 expression. Compared to human control subjects, patients with AS exhibited decreased VEGF165 expression in the endometrium along with increased fibrotic marker expression and collagen production. A fibrotic phenotype was shown in both mice with conditional VEGF reduction and VEGF165-deleted endometrial stromal cells. Exogenous VEGF165 could suppress TGFβ1-induced α-SMA and collagen 1 expression in human primary endometrial stromal cells. However, this beneficial effect was hindered when the expression of smad7 or Notch4 was inhibited or when Notch signaling was blocked, suggesting that smad7 and Notch4 are essential downstream molecules for VEGFA functioning. Overall, our results uncover a clinical targeting strategy for VEGF165 to inhibit pro-fibrotic differentiation of stromal cells by inducing DLL4/Notch4/smad7, which paves the way for AS treatment.

Sign in / Sign up

Export Citation Format

Share Document