collagen formation
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Author(s):  
Xiao-xu Yang ◽  
Zhen-yu Zhao

Cardiac fibrosis is one of the major pathological characteristics of diabetic cardiomyopathy (DCM). MicroRNAs (miRNAs, miRs) have been identified as key regulators in the progression of cardiac fibrosis. This study aimed to investigate the role of miR-30a-5p in DCM and the underlying mechanism. The rat model of diabetes mellitus (DM) was established by streptozotocin injection, and the rat primary cardiac fibroblasts (CFs) were isolated from cardiac tissue and then treated with high glucose (HG). MTT assay was performed to assess the viability of CFs. Dual-luciferase reporter gene assay was conducted to verify the interaction between miR-30a-5p and Smad2. The expression of miR-30a-5p was downregulated in the myocardial tissues of DM rats and HG-stimulated CFs. Overexpression of miR-30a-5p reduced Smad2 levels and inhibited collagen formation in HG-stimulated CFs and DM rats, as well as decreased the proliferation of CFs induced by HG. Smad2 was a target of miR-30a-5p and its expression was inhibited by miR-30a-5p. Furthermore, the simultaneous overexpression of Smad2 and miR-30a-5p reversed the effect of miR-30a-5p overexpression alone in CFs. Our results indicated that miR-30a-5p reduced Smad2 expression and also induced a decrease in proliferation and collagen formation in DCM.


2022 ◽  
Author(s):  
Waresi Tuersong ◽  
Caixian Zhou ◽  
Simin WU ◽  
Peixi Qin ◽  
Chunqun Wang ◽  
...  

Abstract Background: Ivermectin (IVM) is one of the most important and widely used anthelmintics in veterinary medicine. However, its efficacy is increasingly compromised by widespread resistance, and the exact mechanism of IVM resistance remains unclear for most parasitic nematodes including Haemonchus contortus, a blood-sucking parasitic nematode of small ruminants.Methods: In this study, we isolated and assessed an IVM resistant strain from Zhaosu, Xinjiang, China. Subsequently, the comparative analyses on transcriptomics of IVM susceptible and resistant H. contortus adult worms were carried out using RNA sequencing and bioinformatics.Results: In total, 543 and 359 differentially expressed genes (DEGs) were identified in male and female adult worms of the resistant strain compared with the susceptible strain, respectively. The DEGs encode molecules involved in receptor activities, transport, detoxification, lipid metabolism and cuticle collagen formation. In addition, Gene Ontology (GO) analysis revealed that transcriptional changes were dominant in genes associated with ligand-gated channel activity, oxidation-reduction process, lipid metabolic process, and structural constituent of cuticle. The results support previous proposal that the IVM resistant mechanism of H. contortus involved in both neuromuscular and non-neuromuscular pathways. Finally, the quantitative RT-PCR results confirmed that the transcriptional profiles of selected DEGs (male: 8 genes, female: 10 genes) were consistent with those obtained by the RNA-Seq.Conclusions: The findings from this work provided valuable information for further studies on the IVM resistance in H. contortus.


Author(s):  
Chongyang Zhang ◽  
Amy Mohan ◽  
Hangchuan Shi ◽  
Chen Yan

Background cGMP‐hydrolyzing phosphodiesterase type 5 (PDE5) regulates vascular smooth muscle cell (SMC) contraction by antagonizing cGMP‐dependent protein kinase I (PKGI)–dependent SMC relaxation. SMC contractile dysfunction is implicated in the pathogenesis of aortic aneurysm. PDE5 inhibitors have been used for treating erectile dysfunction, such as drug Viagra (sildenafil). However, a few clinical cases have reported the association of Viagra usage with aortic dissection, and reduced PDE5A expression was found in human aortic aneurysm tissues. Therefore, we aimed to investigate the effect of sildenafil on experimental abdominal aortic aneurysm (AAA), the most common form of aortic aneurysm in elderly men. Methods and Results AAA was induced in C57BL/6J male mice by periaortic elastase in combination with blocking elastin/collagen formation via 3‐aminopropionitrile fumarate salt for 35 days. PDE5A protein levels detected by immunostaining were significantly reduced in mouse AAA. Sildenafil application in drinking water significantly aggravated aortic wall dilation and elastin degradation with pre‐existing moderate AAA. The phosphorylation level of myosin light chain 2 at Ser19, a biochemical marker of SMC contraction, was significantly reduced by sildenafil in AAA. Proximity ligation assay further revealed that the interaction between cGMP and PKGI was significantly increased by sildenafil in AAA, suggesting an elevation of PKGI activation in AAA. Conclusions Sildenafil treatment aggravated the degradation of elastin fibers and progression of experimental AAA by dysregulating cGMP and contractile signaling in SMCs. Our findings may raise the caution of clinical usage of Viagra in aneurysmal patients.


2022 ◽  
Vol 23 (1) ◽  
pp. 491
Author(s):  
Aida Șelaru ◽  
Hildegard Herman ◽  
George Mihail Vlăsceanu ◽  
Sorina Dinescu ◽  
Sami Gharbia ◽  
...  

Over the years, natural-based scaffolds have presented impressive results for bone tissue engineering (BTE) application. Further, outstanding interactions have been observed during the interaction of graphene oxide (GO)-reinforced biomaterials with both specific cell cultures and injured bone during in vivo experimental conditions. This research hereby addresses the potential of fish gelatin/chitosan (GCs) hybrids reinforced with GO to support in vitro osteogenic differentiation and, further, to investigate its behavior when implanted ectopically. Standard GCs formulation was referenced against genipin (Gp) crosslinked blend and 0.5 wt.% additivated GO composite (GCsGp/GO 0.5 wt.%). Pre-osteoblasts were put in contact with these composites and induced to differentiate in vitro towards mature osteoblasts for 28 days. Specific bone makers were investigated by qPCR and immunolabeling. Next, CD1 mice models were used to assess de novo osteogenic potential by ectopic implantation in the subcutaneous dorsum pocket of the animals. After 4 weeks, alkaline phosphate (ALP) and calcium deposits together with collagen synthesis were investigated by biochemical analysis and histology, respectively. Further, ex vivo materials were studied after surgery regarding biomineralization and morphological changes by means of qualitative and quantitative methods. Furthermore, X-ray diffraction and Fourier-transform infrared spectroscopy underlined the newly fashioned material structuration by virtue of mineralized extracellular matrix. Specific bone markers determination stressed the osteogenic phenotype of the cells populating the material in vitro and successfully differentiated towards mature bone cells. In vivo results of specific histological staining assays highlighted collagen formation and calcium deposits, which were further validated by micro-CT. It was observed that the addition of 0.5 wt.% GO had an overall significant positive effect on both in vitro differentiation and in vivo bone cell recruitment in the subcutaneous region. These data support the GO bioactivity in osteogenesis mechanisms as being self-sufficient to elevate osteoblast differentiation and bone formation in ectopic sites while lacking the most common osteoinductive agents.


2021 ◽  
Vol 23 (1) ◽  
pp. 91
Author(s):  
Tomasz P. Lehmann ◽  
Urszula Guderska ◽  
Klaudia Kałek ◽  
Maria Marzec ◽  
Agnieszka Urbanek ◽  
...  

This article describes several recent examples of miRNA governing the regulation of the gene expression involved in bone matrix construction. We present the impact of miRNA on the subsequent steps in the formation of collagen type I. Collagen type I is a main factor of mechanical bone stiffness because it constitutes 90–95% of the organic components of the bone. Therefore, the precise epigenetic regulation of collagen formation may have a significant influence on bone structure. We also describe miRNA involvement in the expression of genes, the protein products of which participate in collagen maturation in various tissues and cancer cells. We show how non-collagenous proteins in the extracellular matrix are epigenetically regulated by miRNA in bone and other tissues. We also delineate collagen mineralisation in bones by factors that depend on miRNA molecules. This review reveals the tissue variability of miRNA regulation at different levels of collagen maturation and mineralisation. The functionality of collagen mRNA regulation by miRNA, as proven in other tissues, has not yet been shown in osteoblasts. Several collagen-regulating miRNAs are co-expressed with collagen in bone. We suggest that collagen mRNA regulation by miRNA could also be potentially important in bone metabolism.


Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1884
Author(s):  
Wellison J. S. Diniz ◽  
Gerd Bobe ◽  
Joseph J. Klopfenstein ◽  
Yunus Gultekin ◽  
T. Zane Davis ◽  
...  

Selenium (Se) is an essential micronutrient for growth and immune function in beef cattle. We previously showed that supranutritional maternal organic Se supplementation during late pregnancy improves immune function in their newborn calves; however, the effects of maternal organic Se-supplementation on fetal programming during different pregnancy stages have yet to be elucidated. Herein, we investigated the effects of supranutritional maternal organic Se-supplementation in different pregnancy trimesters on their beef calf’s genome-wide transcriptome profiles. Within 12 to 48 h of birth, whole blood and Longissimus dorsi (LD) muscle biopsies were collected from calves born to 40 crossbred Angus cows that received, except for the control group (CTR), Se-yeast boluses (105 mg of Se/wk) during the first (TR1), second (TR2), or third (TR3) trimester of gestation. Whole-blood Se concentrations of newborn calves increased from CTR, TR1, TR2 to TR3, whereas muscle Se concentrations of newborn calves were only increased in TR3 group. We identified 3048 unique differentially expressed genes (DEGs) across all group comparisons (FDR ≤ 0.05 and |log2FC| ≥ 1.5). Furthermore, we predicted 237 unique transcription factors that putatively regulate the DEGs. Independent of supplementation trimester, supranutritional maternal organic Se supplementation downregulated genes involved in adaptive immunity in all trimesters. Dependent on supplementation trimester, genes involved in muscle development were upregulated by TR3 Se supplementation and downregulated by TR1 Se-supplementation, and genes involved in collagen formation were downregulated by TR2 Se-supplementation. Supranutritional maternal organic Se supplementation in the last trimester of pregnancy resulted in upregulation of myosin and actin filament associated genes, potentially allowing for optimal muscle function and contraction. Our findings suggest a beneficial effect of supranutritional maternal organic Se supplementation during late gestation on Se-status and muscle development and function of newborn calves.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Henrik Jessen ◽  
Nils Hoyer ◽  
Thomas S. Prior ◽  
Peder Frederiksen ◽  
Sarah R. Rønnow ◽  
...  

Abstract Background Remodeling of the extracellular matrix (ECM) is a central mechanism in the progression of idiopathic pulmonary fibrosis (IPF), and remodeling of type VI collagen has been suggested to be associated with disease progression. Biomarkers that reflect and predict the progression of IPF would provide valuable information for clinicians when treating IPF patients. Methods Two serological biomarkers reflecting formation (PRO-C6) and degradation (C6M) of type VI collagen were evaluated in a real-world cohort of 178 newly diagnoses IPF patients. All patients were treatment naïve at the baseline visit. Blood samples and clinical data were collected from baseline, six months, and 12 months visit. The biomarkers were measured by competitive ELISA using monoclonal antibodies. Results Patients with progressive disease had higher (P = 0.0099) serum levels of PRO-C6 compared to those with stable disease over 12 months with an average difference across all timepoints of 12% (95% CI 3–22), whereas C6M levels tended (P = 0.061) to be higher in patients with progressive disease compared with stable patients over 12 months with an average difference across all timepoints of 12% (95% CI − 0.005–27). Patients who did not receive antifibrotic medicine had a greater increase of C6M (P = 0.043) compared to treated patients from baseline over 12 months with an average difference across all timepoints of 12% (95% CI − 0.07–47). There were no differences in biomarker levels between patients receiving pirfenidone or nintedanib. Conclusions Type VI collagen formation was related to progressive disease in patients with IPF in a real-world cohort and antifibrotic therapy seemed to affect the degradation of type VI collagen. Type VI collagen formation and degradation products might be potential biomarkers for disease progression in IPF.


2021 ◽  
Vol 11 (9) ◽  
pp. 828-840
Author(s):  
L. Kupriianova ◽  
A. Pakhlivanzade

In the following article we are going to provide the results of research on uterus’ structure in case of fetuses with a gestational term of 21-28 weeks from mothers, whose pregnancy was complicated by PE of different severity stage (15 cases) comparing to one in case of fetuses from mothers with a physiological pregnancy (15 cases). All fetuses have died intranatally as a result of an acute disorder in uterine-placental and uterine-fetal circulation. The research methods: macroscopic, organometric, histological, immunohistochemical, morphometric and statictical. By applying an organometric method we have revealed a probable decrease of indexes of weight, length and thickness of the uterine’ wall in case of fetuses from mothers with PE comparing to ones in case of fetuses from healthy mothers. The observative histological research had not revealed any significant changes in the strucutre of the organs’ wall in case of fetuses from the study groups. Thus, all organs were represented by mucous, muscular and serous membranes with a clear boundary between them. The comparative morphometric research had revealed the following features of the uterus’ wall structure in case of fetuses from mothers with PE. The indexes of thickness of all structural components of the organ’s wall were clearly decreased comparing to ones in case of fetuses from mothers with a physiological pregnancy. In the uterine endometrium of fetuses from mothers with PE of moderate stage of severity the features of proliferative (hormonal) activity are taking place, however, in the meanwhile, in case of organs of fetuses from mothers with PE of severe stage of severity we could notice a probable decrease of glands’ number as well as a lack of a proliferative activity in them (hypoplastic changes). By applying immunohistochemical method with using MCAT to CD 95 we have disclosed a probable increase of an apoptotic index in organs of fetuses from mothers with a complicated pregnancy towards one in case of fetuses from healthy mothers. Among the specific features of the uterine myometrium strucutre in case of fetuses from mothers with PE we could name the following ones: decrease of the vascular component percentage as well as increase growth of the connective tissue. Moreover, the structure of the connective tissue is represented mostly by the collagen of the III type, while, in case of organs of fetuses from healthy mothers the collagen of the I type prevails. In walls of the vessels of arterial type in case of uterus of fetuses from mothers with PE we could notice an increased glow of the collagen of the III type as well as a probable decrease of glow in case of collagen of the IV type. However, in case of organs’ vessels of fetuses from healthy mothers we could notice an increse of glow of the collagen of the IV type. There is a fact, which attracts an attention to it. Namely, all aforementioned changes in the uterine wall in case of fetuses from mothers with PE are minimally manifested, when the mild course of disease took place, and was maximally manifested in case of severe one. All changes in the uterus in case of fetuses from mothers with PE of different stage of severity, that were postulated above, could contribute to formation of glanduar hyperplasia, endometrial polyps, precancerous diseases as well as endometrial cancer in the subsequent ontogenesis, as well as it could lead to impaired pregnancy and infertility. All aforementioned changes in organs of fetuses from mothers, whose pregnancy was complicated by PE of different stage of severity, were connected with changes in the vascular bed of the mother-placenta-fetus system as well as with endocrine disorders, that take place in case of this pathology, in the organism of pregnant woman.


Cosmetics ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 92
Author(s):  
Nikolay N. Potekaev ◽  
Olga B. Borzykh ◽  
German V. Medvedev ◽  
Marina M. Petrova ◽  
Oksana A. Gavrilyuk ◽  
...  

One of the most important functions of the skin, i.e., protection from mechanical damage, is ensured by collagen fibers and their interaction with other elements in the extracellular matrix. Collagen fiber turnover is a complex multi-stage process. At each stage, a disruption may occur, leading to a decrease in the mechanical properties of the connective tissue. Clinically, collagen formation disorders manifest themselves as increased flabbiness and looseness of the skin and as early signs of facial aging. In addition to the clinical picture, it is important for cosmetologists and dermatologists to understand the etiology and pathogenesis of collagenopathies. In our review, we summarized and systematized the available information concerning the role of genetic and epigenetic factors in skin collagen fiber turnover. Furthermore, we focused on the functions of different types of collagens present in the skin. Understanding the etiology of impaired collagen formation can allow doctors to prescribe pathogenetically based treatments, achieve the most effective results, and minimize adverse reactions.


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