scholarly journals Glia-derived exosomal miR-274 targets Sprouty in trachea and synaptic boutons to modulate growth and responses to hypoxia

2019 ◽  
Author(s):  
Yi-Wei Tsai ◽  
Hsin-Ho Sung ◽  
Jian-Chiuan Li ◽  
Chun-Yen Yeh ◽  
Pei-Yi Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Null Mutant ◽  
Physiological Functions ◽  
Exosome Biogenesis ◽  
Exosomal Mirnas ◽  
Organ Tissue ◽  
Synaptic Boutons ◽  
And Function

AbstractSecreted exosomal miRNAs mediate inter-organ/tissue communication by downregulating gene expression, thereby modulating developmental and physiological functions. However, the source, route, and function have not been formally established for specific miRNAs. Here, we show that glial miR-274 non-cell autonomously modulates the growth of synaptic boutons and tracheal branches. Whereas precursor miR-274 was expressed in glia, mature miR-274 was secreted. miR-274 secretion to circulating hemolymph was detected in exosomes, a process requiring ESCRT components in exosome biogenesis and Rab11 and Syx1A in exosome release. miR-274 downregulated Sprouty to activate MAPK in synaptic boutons and tracheal branches, thereby promoting their growth. Expression of miR-274 solely in glia of a mir-274 null mutant reset normal levels of Sprouty and MAPK, and hemolymphatic exosomal miR-274. mir-274 mutant larvae were hypersensitive to hypoxia, which was suppressed by increasing tracheal branches. Thus, glia-derived miR-274 coordinates growth of synaptic boutons and tracheal branches to modulate larval hypoxia responses.

scholarly journals Glia-derived exosomal miR-274 targets Sprouty in trachea and synaptic boutons to modulate growth and responses to hypoxia

2019 ◽  
Vol 116 (49) ◽  
pp. 24651-24661 ◽  
Author(s):  
Yi-Wei Tsai ◽  
Hsin-Ho Sung ◽  
Jian-Chiuan Li ◽  
Chun-Yen Yeh ◽  
Pei-Yi Chen ◽  
...  
Keyword(s):  
Cell Growth ◽  
Target Cell ◽  
Target Gene ◽  
Mapk Signaling ◽  
Target Cells ◽  
Null Mutant ◽  
Specific Expression ◽  
Exosome Biogenesis ◽  
Synaptic Boutons ◽  
And Function

Secreted exosomal microRNAs (miRNAs) mediate interorgan/tissue communications by modulating target gene expression, thereby regulating developmental and physiological functions. However, the source, route, and function in target cells have not been formally established for specific miRNAs. Here, we show that glial miR-274 non-cell-autonomously modulates the growth of synaptic boutons and tracheal branches. Whereas the precursor form of miR-274 is expressed in glia, the mature form of miR-274 distributes broadly, including in synaptic boutons, muscle cells, and tracheal cells. Mature miR-274 is secreted from glia to the circulating hemolymph as an exosomal cargo, a process requiring ESCRT components in exosome biogenesis and Rab11 and Syx1A in exosome release. We further show that miR-274 can function in the neurons or tracheal cells to modulate the growth of synaptic boutons and tracheal branches, respectively. Also, miR-274 uptake into the target cells by AP-2–dependent mechanisms modulates target cell growth. In the target cells, miR-274 down-regulates Sprouty (Sty) through a targeting sequence at the sty 3′ untranslated region, thereby enhancing MAPK signaling and promoting cell growth. miR-274 expressed in glia of an mir-274 null mutant is released as an exosomal cargo in the circulating hemolymph, and such glial-specific expression resets normal levels of Sty and MAPK signaling and modulates target cell growth. mir-274 mutant larvae are hypersensitive to hypoxia, which is suppressed by miR-274 expression in glia or by increasing tracheal branches. Thus, glia-derived miR-274 coordinates growth of synaptic boutons and tracheal branches to modulate larval hypoxia responses.

scholarly journals Exosome biogenesis, secretion and function of exosomal miRNAs in skeletal muscle myogenesis

2020 ◽  
Vol 53 (7) ◽  
Author(s):  
Binglin Yue ◽  
Haiyan Yang ◽  
Jian Wang ◽  
Wenxiu Ru ◽  
Jiyao Wu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exosome Biogenesis ◽  
Exosomal Mirnas ◽  
And Function

Xenotransplantation for Liver Therapy Or: Can Porcine Hepatocytes Generate Physiological Functions Sufficient for a Human Patient in ALF?

2002 ◽  
Vol 25 (10) ◽  
pp. 1019-1028 ◽  
Author(s):  
C. Hammer
Keyword(s):  
Culture Conditions ◽  
Detailed Knowledge ◽  
Human Patient ◽  
Physiological Functions ◽  
Organ Tissue ◽  
Set Up ◽  
And Function ◽  
Cell Culture Conditions ◽  
Porcine Hepatocytes ◽  
Selection Of

Detailed knowledge about physiology, biochemistry and function is required before artificial liver devices using porcine hepatocytes may be used successfully. Improvement of cell culture conditions and tissue engineering may permit the generation of human hepatocytes as substitutes for grafts in a transplantation setting. The physiological functions of xenografts have to be compatible with those of the recipient. However, first observations indicate that most physiological interaction in widely divergent species combinations such as pig and man are considerably different. This may be crucial for the selection of a suitable organ, tissue or cell for a clinical set-up. These differences vary from organ to organ and cell to cell. Only very conservative molecules, like for example insulin or calcitonin function properly in both species, while others such as complement, albumin and erythropoietin do not fulfill their task properly or not at all.

scholarly journals Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 350
Author(s):  
Julianty Frost ◽  
Mark Frost ◽  
Michael Batie ◽  
Hao Jiang ◽  
Sonia Rocha
Keyword(s):  
Gene Expression ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Regulator ◽  
Hydroxylase Activity ◽  
Control Of Gene Expression ◽  
Prolyl Hydroxylases ◽  
Chromatin Organisation ◽  
Sense And Respond ◽  
Almost All ◽  
And Function

Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health.

scholarly journals Testicular Melatonin and Its Pathway in Roe Deer Bucks (Capreolus capreolus) during Pre- and Post-Rut Periods: Correlation with Testicular Involution

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1874
Author(s):  
Alberto Elmi ◽  
Nadia Govoni ◽  
Augusta Zannoni ◽  
Martina Bertocchi ◽  
Chiara Bernardini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Correlation Analysis ◽  
Roe Deer ◽  
Capreolus Capreolus ◽  
Reproductive Activity ◽  
Melatonin Receptors ◽  
Local Synthesis ◽  
Testicular Weight ◽  
And Function ◽  
Gene Expression Levels

Roe deer are seasonal breeders with a complete yearly testicular cycle. The peak in reproductive activity is recorded during summer, the rutting period, with the highest levels of androgens and testicular weight. Melatonin plays a pivotal role in seasonal breeders by stimulating the hypothalamus–pituitary–gonads axis and acting locally; in different species, its synthesis within testes has been reported. The aim of this study was to evaluate the physiological melatonin pattern within roe deer testes by comparing data obtained from animals sampled during pre- and post-rut periods. Melatonin was quantified in testicular parenchyma, along with the genetic expression of enzymes involved in its local synthesis (AANAT and ASMT) and function (UCP1). Melatonin receptors, MT1-2, were quantified both at protein and gene expression levels. Finally, to assess changes in reproductive hormonal profiles, testicular dehydroepiandrosterone (DHEA) was quantified and used for a correlation analysis. Melatonin and AANAT were detected in all samples, without significant differences between pre- and post-rut periods. Despite DHEA levels confirming testicular involution during the post-rut period, no correlations appeared between such involution and melatonin pathways. This study represents the first report regarding melatonin synthesis in roe deer testes, opening the way for future prospective studies in the physiology of this species.

scholarly journals Micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and secretion to improve osseointegration

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhengchuan Zhang ◽  
Ruogu Xu ◽  
Yang Yang ◽  
Chaoan Liang ◽  
Xiaolin Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Titanium Surface ◽  
Titanium Implants ◽  
Extracellular Secretion ◽  
Exosome Biogenesis ◽  
Marrow Mesenchymal Stem Cells ◽  
Proliferation In Vitro ◽  
Extracellular Environment

Abstract Background Micro/nano-textured hierarchical titanium topography is more bioactive and biomimetic than smooth, micro-textured or nano-textured titanium topographies. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs play important roles in the osseointegration of titanium implants, but the effects and mechanisms of titanium topography on BMSCs-derived exosome secretion are still unclear. This study determined whether the secretion behavior of exosomes derived from BMSCs is differently affected by different titanium topographies both in vitro and in vivo. Results We found that both micro/nanonet-textured hierarchical titanium topography and micro/nanotube-textured hierarchical titanium topography showed favorable roughness and hydrophilicity. These two micro/nano-textured hierarchical titanium topographies enhanced the spreading areas of BMSCs on the titanium surface with stronger promotion of BMSCs proliferation in vitro. Compared to micro-textured titanium topography, micro/nano-textured hierarchical titanium topography significantly enhanced osseointegration in vivo and promoted BMSCs to synthesize and transport exosomes and then release these exosomes into the extracellular environment both in vitro and in vivo. Moreover, micro/nanonet-textured hierarchical titanium topography promoted exosome secretion by upregulating RAB27B and SMPD3 gene expression and micro/nanotube-textured hierarchical titanium topography promoted exosome secretion due to the strongest enhancement in cell proliferation. Conclusions These findings provide evidence that micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and extracellular secretion for enhanced osseointegration. Our findings also highlight that the optimized titanium topography can increase exosome secretion from BMSCs, which may promote osseointegration of titanium implants.

scholarly journals Commuting to Work: Nucleolar Long Non-Coding RNA Control Ribosome Biogenesis from Near and Far

2021 ◽  
Vol 7 (3) ◽  
pp. 42
Author(s):  
Victoria Mamontova ◽  
Barbara Trifault ◽  
Lea Boten ◽  
Kaspar Burger
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Ribosome Biogenesis ◽  
Intergenic Spacer ◽  
Cellular Growth ◽  
Rrna Synthesis ◽  
Protein Coding ◽  
Non Coding Rna ◽  
And Function ◽  
In Cis

Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism. The nucleolus is a prime example of how different lncRNA species concomitantly regulate gene expression by facilitating the production and processing of ribosomal (r)RNA for ribosome biogenesis. Here, we summarise the current findings on how RNAPII influences nucleolar structure and function. We describe how RNAPII-dependent lncRNA can both promote nucleolar integrity and inhibit ribosomal (r)RNA synthesis by modulating the availability of rRNA synthesis factors in trans. Surprisingly, some lncRNA transcripts can directly originate from nucleolar loci and function in cis. The nucleolar intergenic spacer (IGS), for example, encodes nucleolar transcripts that counteract spurious rRNA synthesis in unperturbed cells. In response to DNA damage, RNAPII-dependent lncRNA originates directly at broken ribosomal (r)DNA loci and is processed into small ncRNA, possibly to modulate DNA repair. Thus, lncRNA-mediated regulation of nucleolar biology occurs by several modes of action and is more direct than anticipated, pointing to an intimate crosstalk of RNA metabolic events.

scholarly journals (Pro)renin receptor: another member of the system controlled by angiotensin II?

2011 ◽  
Vol 13 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Luciana G Pereira ◽  
Carine P Arnoni ◽  
Edgar Maquigussa ◽  
Priscila C Cristovam ◽  
Juliana Dreyfuss ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Mesangial Cells ◽  
At1 Receptor ◽  
Receptor Internalization ◽  
Prorenin Receptor ◽  
Receptor Blockers ◽  
And Function ◽  
At1 Receptor Blockers

The prorenin receptor [(P)RR] is upregulated in the diabetic kidney and has been implicated in the high glucose (HG)-induced overproduction of profibrotic molecules by mesangial cells (MCs), which is mediated by ERK1/2 phosphorylation. The regulation of (P)RR gene transcription and the mechanisms by which HG increases (P)RR gene expression are not fully understood. Because intracellular levels of angiotensin II (AngII) are increased in MCs stimulated with HG, we used this in vitro system to evaluate the possible role of AngII in (P)RR gene expression and function by comparing the effects of AT1 receptor blockers (losartan or candesartan) and (P)RR mRNA silencing (siRNA) in human MCs (HMCs) stimulated with HG. HG induced an increase in (P)RR and fibronectin expression and in ERK1/2 phosphorylation. These effects were completely reversed by (P)RR siRNA and losartan but not by candesartan (an angiotensin receptor blocker that, in contrast to losartan, blocks AT1 receptor internalization). These results suggest that (P)RR gene activity may be controlled by intracellular AngII and that HG-induced ERK1/2 phosphorylation and fibronectin overproduction are primarily induced by (P)RR activation. This relationship between AngII and (P)RR may constitute an additional pathway of MC dysfunction in response to HG stimulation.

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