Role of Retinoids in Spermatogonial Proliferation and Differentiation and the Meiotic Prophase

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.

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Increased Expression of Retinol-Binding Protein 4 in Ovarian Endometrioma and Its Possible Role in the Pathogenesis of Endometriosis

International Journal of Molecular Sciences ◽

10.3390/ijms22115827 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5827

Author(s):

Jae Chul Lee ◽

Sung Hoon Kim ◽

Young Sang Oh ◽

Ju Hee Kim ◽

Sa Ra Lee ◽

...

Keyword(s):

Retinol Binding Protein ◽

Endometrial Stromal Cells ◽

Endometrial Cells ◽

Retinol Binding Protein 4 ◽

Ovarian Endometrioma ◽

Proliferation And Differentiation ◽

In Vitro Effects ◽

Ovarian Endometriomas

Although endometriosis is a benign disease characterized by the presence of endometrial tissues outside the uterus, ectopic endometrial cells can exhibit malignant biological behaviors. Retinol-binding protein4 (RBP4) is a novel adipocyte-derived cytokine, which has important roles in regulating insulin sensitivity and energy metabolism. RBP4 is a potent modulator of gene transcription, and acts by directly controlling cell growth, invasiveness, proliferation and differentiation. Here, we evaluated the possible role of RBP4 in the pathogenesis of endometriosis. We compared the levels of RBP4 in the tissues and peritoneal fluid (PF) of women with and without endometriosis and evaluated the in vitro effects of RBP4 on the viability, invasiveness, and proliferation of endometrial stromal cells (ESCs). RBP4 levels were significantly higher in the PF of the women in the endometriosis group than in the controls. RBP4 immunoreactivity was significantly higher in the ovarian endometriomas of women with advanced stage endometriosis than those of controls. In vitro treatment with human recombinant-RBP4 significantly increased the viability, bromodeoxyuridine expression, and invasiveness of ESCs. Transfection with RBP4 siRNA significantly reduced ESC viability and invasiveness. These findings suggest that RBP4 partakes in the pathogenesis of endometriosis by increasing the viability, proliferation and invasion of endometrial cells.

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Differential role of the estrogen receptors ESR1 and ESR2 on the regulation of proteins involved with proliferation and differentiation of Sertoli cells from 15-day-old rats

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2013.09.015 ◽

2014 ◽

Vol 382 (1) ◽

pp. 84-96 ◽

Cited By ~ 32

Author(s):

Thaís F.G. Lucas ◽

Maria Fatima M. Lazari ◽

Catarina S. Porto

Keyword(s):

Estrogen Receptors ◽

Sertoli Cells ◽

Proliferation And Differentiation ◽

Old Rats

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Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

Molecules ◽

10.3390/molecules26020309 ◽

2021 ◽

Vol 26 (2) ◽

pp. 309

Author(s):

Lijing Yang ◽

Mengjia Hu ◽

Yukai Lu ◽

Songling Han ◽

Junping Wang

Keyword(s):

Purinergic Receptors ◽

Therapeutic Potential ◽

Inflammasome Activation ◽

Hematopoietic Stem ◽

Hematopoietic Transplantation ◽

Proliferation And Differentiation ◽

Extracellular Stimuli ◽

Transplantation Complications ◽

Underlying Mechanisms

Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies.

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Gab1 and SHP-2 promote Ras/MAPK regulation of epidermal growth and differentiation

The Journal of Cell Biology ◽

10.1083/jcb.200205017 ◽

2002 ◽

Vol 159 (1) ◽

pp. 103-112 ◽

Cited By ~ 57

Author(s):

Ti Cai ◽

Keigo Nishida ◽

Toshio Hirano ◽

Paul A. Khavari

Keyword(s):

Epidermal Cell ◽

Mapk Signaling ◽

Dominant Negative ◽

Mapk Activity ◽

Ras Activation ◽

Proliferation And Differentiation ◽

Epidermal Proliferation ◽

Epidermal Growth ◽

Docking Protein

În epidermis, Ras can influence proliferation and differentiation; however, regulators of epidermal Ras function are not fully characterized, and Ras effects on growth and differentiation are controversial. EGF induced Ras activation in epidermal cells along with phosphorylation of the multisubstrate docking protein Gab1 and its binding to SHP-2. Expression of mutant Gab1Y627F deficient in SHP-2 binding or dominant-negative SHP-2C459S reduced basal levels of active Ras and downstream MAPK proteins and initiated differentiation. Differentiation triggered by both Gab1Y627F and SHP-2C459S could be blocked by coexpression of active Ras, consistent with Gab1 and SHP-2 action upstream of Ras in this process. To study the role of Gab1 and SHP-2 in tissue, we generated human epidermis overexpressing active Gab1 and SHP-2. Both proteins stimulated proliferation. In contrast, Gab1Y627F and SHP-2C459S inhibited epidermal proliferation and enhanced differentiation. Consistent with a role for Gab1 and SHP-2 in sustaining epidermal Ras/MAPK activity, Gab1−/− murine epidermis displayed lower levels of active Ras and MAPK with postnatal Gab1−/− epidermis, demonstrating the hypoplasia and enhanced differentiation seen previously with transgenic epidermal Ras blockade. These data provide support for a Ras role in promoting epidermal proliferation and opposing differentiation and indicate that Gab1 and SHP-2 promote the undifferentiated epidermal cell state by facilitating Ras/MAPK signaling.

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Expression and localization of the mRNA for DNA (cytosine-5)- methyltransferase in mouse seminiferous tubules.

Journal of Histochemistry & Cytochemistry ◽

10.1177/42.9.8064134 ◽

1994 ◽

Vol 42 (9) ◽

pp. 1271-1276 ◽

Cited By ~ 14

Author(s):

M Numata ◽

T Ono ◽

S Iseki

Keyword(s):

In Situ Hybridization ◽

Significant Role ◽

Meiotic Prophase ◽

Oligonucleotide Probe ◽

Mouse Testis ◽

Seminiferous Tubules ◽

Hybridization Histochemistry ◽

In Situ Hybridization Histochemistry

DNA (cytosine-5)-methyltransferase (DNA MTase) is the only enzyme known to be involved in the methylation of mammalian DNA. Although the expression of DNA MTase gene is abundant in the testis, little is known about the role of this enzyme during spermatogenesis. We examined the distribution of DNA MTase mRNA in mouse testis by in situ hybridization histochemistry with an oligonucleotide probe. The mRNA signal was observed in the seminiferous tubules and was localized predominantly in spermatogonia and spermatocytes, particularly during the earlier steps of meiotic prophase I, with maximal intensity in the early pachytene cells. These results suggest some significant role for DNA MTase in spermatogenesis.

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Role of keratinocyte-derived factors involved in regulating the proliferation and differentiation of mammalian epidermal melanocytes

Pigment Cell Research ◽

10.1111/j.1600-0749.2004.00198.x ◽

2005 ◽

Vol 18 (1) ◽

pp. 2-12 ◽

Cited By ~ 192

Author(s):

Tomohisa Hirobe

Keyword(s):

Proliferation And Differentiation

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An oligomer complementary to c-myc mRNA inhibits proliferation of HL-60 promyelocytic cells and induces differentiation

Molecular and Cellular Biology ◽

10.1128/mcb.8.2.963-973.1988 ◽

1988 ◽

Vol 8 (2) ◽

pp. 963-973

Author(s):

J T Holt ◽

R L Redner ◽

A W Nienhuis

Keyword(s):

Cell Growth ◽

Protein Concentration ◽

Myeloid Differentiation ◽

Sequence Specificity ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Steady State Levels ◽

Cell Growth And Differentiation ◽

Antisense Oligomer

To study the role of a nuclear proto-oncogene in the regulation of cell growth and differentiation, we inhibited HL-60 c-myc expression with a complementary antisense oligomer. This oligomer was stable in culture and entered cells, forming an intracellular duplex. Incubation of cells with the anti-myc oligomer decreased the steady-state levels of c-myc protein by 50 to 80%, whereas a control oligomer did not significantly affect the c-myc protein concentration. Direct inhibition of c-myc expression with the anti-myc oligomer was associated with a decreased cell growth rate and an induction of myeloid differentiation. Related antisense oligomers with 2- to 12-base-pair mismatches with c-myc mRNA did not influence HL-60 cells. Thus, the effects of the antisense oligomer exhibited sequence specificity, and furthermore, these effects could be reversed by hybridization competition with another complementary oligomer. Antisense inhibition of a nuclear proto-oncogene apparently bypasses cell surface events in affecting cell proliferation and differentiation.

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The role of autophagy in the process of osseointegration around titanium implants with micro-nano topography promoted by osteoimmunity

Scientific Reports ◽

10.1038/s41598-021-98007-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ting Zhang ◽

Mengyang Jiang ◽

Xiaojie Yin ◽

Peng Yao ◽

Huiqiang Sun

Keyword(s):

Titanium Implants ◽

Eukaryotic Cells ◽

Raw264.7 Cells ◽

Control Group ◽

Immune Microenvironment ◽

Promote Cell Proliferation ◽

Osteogenic Markers ◽

Proliferation And Differentiation ◽

Anti Inflammatory

AbstractOsteoimmunity plays an important role in the process of implant osseointegration. Autophagy is a conservative metabolic pathway of eukaryotic cells, but whether the interaction between autophagy and osteoimmunity plays a key role in osseointegration remains unclear. In this study, we prepared smooth titanium disks and micro-nano topography titanium disks, to study the immune microenvironment of RAW264.7 cells, and prepared the conditioned medium to study the effect of immune microenvironment on the osteogenesis and autophagy of MC3T3-E1 cells. Autophagy inhibitor 3-MA was used to inhibit autophagy to observe the change of expression of osteogenic markers. The results showed that the micro-nano topography titanium disks could stimulate RAW264.7 cells to differentiate into M2 type, forming an anti-inflammatory immune microenvironment; compared with the control group, the anti-inflammatory immune microenvironment promoted the proliferation and differentiation of osteoblasts better. The anti-inflammatory immune environment activated the autophagy level of osteoblasts, while the expression of osteogenic markers was down-regulated after inhibition of autophagy. These results indicate that anti-inflammatory immune microenvironment can promote cell proliferation and osteogenic differentiation, autophagy plays an important role in this process. This study further explains the mechanism of implant osseointegration in osteoimmune microenvironment, and provides reference for improving implant osseointegration.

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The Role of the Hedgehog Pathway in Cholangiocarcinoma

Cancers ◽

10.3390/cancers13194774 ◽

2021 ◽

Vol 13 (19) ◽

pp. 4774

Author(s):

Giulia Anichini ◽

Laura Carrassa ◽

Barbara Stecca ◽

Fabio Marra ◽

Chiara Raggi

Keyword(s):

Anticancer Agents ◽

Cell Biology ◽

Detailed Knowledge ◽

Molecular Features ◽

Cell Proliferation And Differentiation ◽

Predominant Type ◽

Proliferation And Differentiation ◽

Cholangiocarcinoma Cell ◽

Hh Signaling

Cholangiocarcinoma (CCA) is a poorly treatable type of cancer and, along with hepatocellular carcinoma (HCC), is the predominant type of primitive liver cancer in adults. The lack of understanding of CCA biology has slowed down the identification of novel targets and the development of effective treatments. While tumors share some general characteristics, detailed knowledge of specific features is essential for the development of effectively tailored therapeutic approaches. The Hedgehog (HH) signaling cascade regulates stemness biology, embryonal development, tissue homeostasis, and cell proliferation and differentiation. Its aberrant activation has been associated with a variety of solid and hematological human malignancies. Several HH-inhibiting compounds have been indeed developed as potential anticancer agents in different types of tumors, with Smoothened and GLI inhibitors showing the most promising results. Beside its well-established function in other tumors, findings regarding the HH signaling in CCA are still controversial. Here we will give an overview of the most important clinical and molecular features of cholangiocarcinoma, and we will discuss the available evidence of the crosstalk between the HH signaling pathway and the cholangiocarcinoma cell biology.

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