Редактирование: COL3A1 (раздел)

==Publications==

{{medline-entry
|title=Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31864349
|abstract=Despite being one of the major causes of infertility in mares, the mechanisms responsible for equine endometrosis are still unclear and controversial. In the last few years, many investigations focused on local immune response modulation. Since it is generally accepted that endometrial fibrosis increases with age, we hypothesize that older mares could show altered local immune modulation, initiating a pro-inflammatory and tissue remodeling cascade of events that could lead to endometrosis. The aim of this study, indeed, is to evaluate and describe the local gene expression of genes involved in acute inflammatory response and fibrosis (COL1A1, [[COL3A1]], TNFA, [[MMP9]], [[IL6]], [[TGFB1]] and TGFBR1), together with others associated to immune modulation ([[DEFB4B]], [[IDO1]] and [[FOXP3]]), in uterine specimens from mares of different age. Twenty-five Standardbred mares were involved in the study with age ranging from 7 to 19 years (mean 10.40 ± 4.42). They were divided by age into two groups: G1 (n = 15, less than 10 years old) and G2 (N = 10, greater than 11 years old). Specimens from the uterus' right horn-body junction were collected and processed for histology evaluation and RT-qPCR assay.Gene expression of [[DEFB4B]], [[MMP9]] and TNFA was higher in younger mares, suggesting a balance in immune modulation and tissue remodeling. Interleukin-6 and [[COL3A1]] gene expressions were greater in older animals, probably indicating inflammatory pathways activation and fibrosis increase. Although no differences in fibrosis and inflammation distribution could be found with histological examination among G1 and G2, our results suggest a possible involvement of DEF4BB in regulating the local immune response in younger mare's uterus (G1); age may contribute to the dis-regulation of [[DEFB4B]] transcription and, indirectly, influence the extracellular matrix homeostasis. Transcription of [[IDO1]] and [[FOXP3]] genes, instead, does not seem to be age related, or to be involved in local immune-response and tissue remodeling functions. Further investigations are needed in order to clarify the interactions between the expression of [[DEFB4B]], [[IL6]], TNFA, [[COL3A1]] and [[MMP9]] and other local signals of immune-modulation and tissue remodeling, in mares in a prospective study design.
|mesh-terms=* Aging
* Animals
* Breeding
* Defensins
* Endometrium
* Female
* Fibrosis
* Gene Expression
* Horses
* Inflammation
* Reverse Transcriptase Polymerase Chain Reaction
|keywords=* Defensin-β
* Endometrium
* Gene expression
* Immune-modulation
* Mare
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925900
}}
{{medline-entry
|title=Collagens and DNA methyltransferases in mare endometrosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31512314
|abstract=Inflammation and fibroproliferative diseases may be modulated by epigenetic changes. Therefore, we suggest that epigenetic mechanisms could be involved in equine endometrosis pathogenesis. DNA methylation is one of the methods to evaluate epigenetics, through the transcription of methyltransferases ([[DNMT1]], [[DNMT3A]], [[DNMT3B]]). The correlation between DNMTs and collagen (COL) transcripts was assessed for the different Kenney and Doig's (Current Therapy in Theriogenology. Philadelphia: WB Saunders; 1986) endometrium categories. Endometrial biopsies were randomly collected from cyclic mares. Histological classification (category I, n = 13; II A, n = 17; II B, n = 12; and III, n = 7) and evaluation of [[COL1A2]], [[COL3A1]] and DNMTs transcripts by qPCR, were performed. Data were analysed by one-way analysis of variance (ANOVA), Kruskal-Wallis test and Pearson correlation. As mares aged, there was an increase in endometrium fibrosis (p < .01), and in [[DNMT1]] mRNA (p < .001). Considering [[DNMT3B]] transcripts for each category, there was an increase with fibrosis (p < .05). No changes were observed for [[DNMT1]] and [[DNMT3A]] transcripts. However, [[DNMT3A]] mRNA levels were the highest in all categories (p < .01). In category I endometrium, a positive correlation was observed for transcripts of all DNMTs in both COLs (p < .01). In category IIA, this correlation was also maintained for all DNMTs transcripts in [[COL1A2]] (p < .05), but only for [[DNMT3B]] in [[COL3A1]] (p < .05). In category IIB, there was a positive correlation between [[DNMT3B]] and [[COL3A1]] (p < .05). In category III, a positive correlation was only observed between [[DNMT3B]] and [[COL3A1]] (p < .05). Our results suggest that there is a disturbance in COLs and DNMTs correlation during fibrosis.
|mesh-terms=* Aging
* Animals
* Collagen
* DNA (Cytosine-5-)-Methyltransferases
* DNA Methylation
* Endometritis
* Endometrium
* Female
* Fibrosis
* Horse Diseases
* Horses
* RNA, Messenger
|keywords=* DNA methylation
* collagen
* endometrium
* epigenetic
* fibrosis
* mare
|full-text-url=https://sci-hub.do/10.1111/rda.13515
}}
{{medline-entry
|title=Reductive Stress Selectively Disrupts Collagen Homeostasis and Modifies Growth Factor-independent Signaling Through the MAPK/Akt Pathway in Human Dermal Fibroblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30890563
|abstract=Redox stress is a well-known contributor to aging and diseases in skin. Reductants such as dithiothreitol (DTT) can trigger a stress response by disrupting disulfide bonds. However, the quantitative response of the cellular proteome to reductants has not been explored, particularly in cells such as fibroblasts that produce extracellular matrix proteins. Here, we have used a robust, unbiased, label-free SWATH-MS proteomic approach to quantitate the response of skin fibroblast cells to DTT in the presence or absence of the growth factor PDGF. Of the 4487 proteins identified, only 42 proteins showed a statistically significant change of 2-fold or more with reductive stress. Our proteomics data show that reductive stress results in the loss of a small subset of reductant-sensitive proteins (including the collagens COL1A1/2 and [[COL3A1]], and the myopathy-associated collagens COL6A1/2/3), and the down-regulation of targets downstream of the MAPK pathway. We show that a reducing environment alters signaling through the PDGF-associated MAPK/Akt pathways, inducing chronic dephosphorylation of ERK1/2 at Thr202/Tyr204 and phosphorylation of Akt at Ser473 in a growth factor-independent manner. Our data highlights collagens as sentinel molecules for redox stress downstream of MAPK/Akt, and identifies intervention points to modulate the redox environment to target skin diseases and conditions associated with erroneous matrix deposition.
|mesh-terms=* Antioxidants
* Collagen
* Dermis
* Dithiothreitol
* Down-Regulation
* Endoplasmic Reticulum Stress
* Extracellular Matrix Proteins
* Fibroblasts
* Homeostasis
* Humans
* Mitogen-Activated Protein Kinases
* Oxidation-Reduction
* Phosphorylation
* Phosphorylcholine
* Platelet-Derived Growth Factor
* Proto-Oncogene Proteins c-akt
* Signal Transduction
|keywords=* Aging
* Chaperone*
* Disulfides*
* Extracellular matrix*
* Label-free quantification
* Oxidative stress
* SWATH-MS
* Signal Transduction*
* Thiol redox chemistry
* protein homeostasis
* skin fibroblasts
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553930
}}
{{medline-entry
|title=Sirtuin 7 is decreased in pulmonary fibrosis and regulates the fibrotic phenotype of lung fibroblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28385812
|abstract=Pulmonary fibrosis is a severe condition with no cure and limited therapeutic options. A better understanding of its pathophysiology is needed. Recent studies have suggested that pulmonary fibrosis may be driven by accelerated aging-related mechanisms. Sirtuins (SIRTs), particularly [[SIRT1]], [[SIRT3]], and [[SIRT6]], are well-known mediators of aging; however, limited data exist on the contribution of sirtuins to lung fibrosis. We assessed the mRNA and protein levels of all seven known sirtuins in primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in comparison with lung fibroblasts from healthy controls. These unbiased tests revealed a tendency for all sirtuins to be expressed at lower levels in fibroblasts from patients compared with controls, but the greatest decrease was observed with [[SIRT7]]. Similarly, [[SIRT7]] was decreased in lung tissues of bleomycin-challenged mice. Inhibition of [[SIRT7]] with siRNA in cultured lung fibroblasts resulted in an increase in collagen and α-smooth muscle actin (α-SMA). Reciprocally, overexpression of [[SIRT7]] resulted in lower basal and TGF-β-induced levels of [[COL1A1]], [[COL1A2]], [[COL3A1]], and α-SMA mRNAs, as well as collagen and α-SMA proteins. Induced changes in [[SIRT7]] had no effect on endogenous TGF-β mRNA levels or latent TGF-β activation, but overexpression of [[SIRT7]] reduced the levels of Smad3 mRNA and protein. In conclusion, the decline in [[SIRT7]] in lung fibroblasts has a profibrotic effect, which is mediated by changes in Smad3 levels.
|mesh-terms=* Actins
* Adult
* Animals
* Cell Nucleus
* Cells, Cultured
* Collagen
* Dermis
* Female
* Fibroblasts
* Gene Silencing
* Humans
* Idiopathic Pulmonary Fibrosis
* Immunohistochemistry
* Infant, Newborn
* Lung
* Mice, Inbred C57BL
* Phenotype
* RNA, Messenger
* Sirtuins
* Smad3 Protein
* Subcellular Fractions
* Transforming Growth Factor beta
|keywords=* SIRT7
* aging
* idiopathic pulmonary fibrosis
* pulmonary fibrosis
* systemic sclerosis
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495944
}}