Age-related lung tissue remodeling due to the local distribution of MMP-2, TIMP-2, TGF-β and Hsp70

Abstract Background: Age-related degeneration of lung tissues increases the risk of lung injury and exacerbates lung disease. It is also the main risk factor for chronic lung diseases (such as COPD, idiopathic pulmonary fibrosis, cancer, etc.).Methods: we performed systematic screening, evaluation of elderly macaque model. A senile multiple organ dysfunction model was used to explored whether BMMSCS could improve degeneration of lung tissues in an elderly macaque model.Results: Using model evaluation tests, we found that the average alveolar area, Mean linear intercept（MLI） and fibrosis area in the elderly macaque models were significantly larger than in young rhesus monkeys (P <0.05), and the capillary density around the alveoli was significantly lower than in young macaque models (P <0.05). Intraveous infusion of BMMSCS reduced the degree of pulmonary fibrosis in elderly macaque, increased the density of capillaries around the alveoli (P <0.05), and the number of type Ⅱ alveolar epithelium in elderly macaque (P <0.05). BMMSCS infusion reduced lung tissue ROS level, systemic and lung tissue inflammation level and Treg cell ratio in elderly macaque model（P＜0.05）. Indirect co-cultivation revealed that BMMSCS reduced the expression of senescence-related genes, ROS levels, apoptosis rate of aging type Ⅱ alveolar epithelial cells (A549 cells) and promoted their proliferation (P＜0.05).Conclusions: BMMSC treatment can improve age-related degeneration of macaque lung tissue

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Age-related differences in the reactivity of the respiratory division of lungs in rats after administration of magnesium chloride

Bulletin physiology and pathology of respiration ◽

10.36604/1998-5029-2021-79-95-102 ◽

2021 ◽

pp. 95-102

Author(s):

R. V. Yanko ◽

E. G. Chaka ◽

M. I. Levashov

Keyword(s):

Lung Function ◽

Lung Tissue ◽

Magnesium Chloride ◽

Standard Diet ◽

Relative Area ◽

Prolonged Administration ◽

Experimental Animals ◽

Functional Changes ◽

Age Related ◽

Old Rats

Introduction. Magnesium is directly involved in the regulation of lung function. However, the effectiveness of various magnesium preparations for activating lung function is not unambiguous. One of the reasons for this may be age-related differences in the nature of structural and functional changes in the lungs in response to the administration of magnesium.Aim. To study the reactivity of the lungs respiratory division of different ages rats to prolonged administration of magnesium chloride.Materials and methods. The experiments were performed on 48 male Wistar rats of 3 and 15 months of age. The experimental animals, in addition to the standard diet, received magnesium chloride at a dose of 50 mg/kg body weight daily for 21 days. At the end of the experiment, lung tissue samples were taken for histomorphological and biochemical studies.Results. At the end of the experiment, 3-month-old rats treated with magnesium chloride showed an increase in the size of the alveoli, a decrease in the relative area of the parenchyma and stroma, and an increase in the relative area of air spaces. A decrease in the thickness of the interalveolar septum and the concentration of oxyproline in the lung tissue of these rats may indicate a decrease in the number of connective tissue elements. In 15- month-old experimental animals, on the contrary, an increase in the relative area of the parenchyma and stroma of the lungs (by 14%), a decrease in the relative area of air spaces (by 12%), and an increase in the concentration of oxyproline in the lungs (by 21%) were observed.Conclusion. Thus, the research results indicate age-related differences in changes in morphological and biochemical parameters characterizing the state of the respiratory division of the lungs with prolonged administration of magnesium chloride. The nature and severity of these changes suggests that in 3-month-old rats magnesium increased lung activity, and in 15-month-old animals, on the contrary, it decreased.

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COPD affected lung tissue remodelling due to the local distribution of MMP-2, TIMP-2, TGF-β1 and HSP-70

Papers on Anthropology ◽

10.12697/poa.2017.26.2.16 ◽

2017 ◽

Vol 26 (2) ◽

pp. 157

Author(s):

Zane Vitenberga ◽

Māra Pilmane ◽

Aurika Babjoniševa

Keyword(s):

Lung Tissue ◽

Matrix Metalloproteinase 2 ◽

Secretory Cells ◽

Control Group ◽

Local Distribution ◽

Hsp 70 ◽

Tissue Remodelling ◽

Regulatory Factors ◽

Airway Mucosa ◽

Tgf Β1

Chronic obstructive pulmonary disease (COPD) is strongly associated with progressive airway limitation where the key mechanism is abnormal airway remodelling of bronchial mucosa maintained by complex crosstalk of tissue remodelling and regulatory factors. The aim of this study was to determine the appearance and local distribution of tissue remodelling factors in COPD-affected lung tissue and to compare the findings with the control group. In this study, lung tissue specimens were obtained from 27 patients with COPD and 49 control patients. Tissue samples were examined by routine hematoxylin and eosin staining. Remodelling and regulatory factors matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), transforming growth factor-β1 (TGF-β1), as well as heat shock protein-70 (Hsp-70) were detected by immunohistochemistry in airway mucosa. The numbers of positive structures were evaluated semiquantitatively. Non-parametrical statistical analysis was performed. Overall COPD-affected lung tissue presented chronic inflammation and tissue remodelling in routine histological analysis. Compared to the control group, statistically significant (P<0.05) difference was calculated between COPD-affected lung tissue and control group with overall more immunoreactive cells containing MMP-2, TIMP-2 and TGF-β1 and less Hsp-70 immunoreactive bronchial epithelial cells, subepithelial connective tissue fibroblasts, bronchial smooth muscle cells and secretory cells of bronchial glands with more pronounced findings of TGF-β1, however, less Hsp-70. Study findings suggest pronounced tissue damage and remodelling with the local regulatory environment of up-regulated TGF-β1. Increased numbers of MMP-2, TIMP-2 and TGF-β1 immunoreactive cells suggest the key role of these remodelling factors in COPD pathogenesis. Decrease of Hsp-70 proves increased cell damage in COPD-affected airway mucosa.

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Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season

BMC Veterinary Research ◽

10.1186/s12917-019-2215-z ◽

2019 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

M. Crociati ◽

S. Capomaccio ◽

M. T. Mandara ◽

G. Stradaioli ◽

L. Sylla ◽

...

Keyword(s):

Immune Response ◽

Immune Modulation ◽

Tissue Remodeling ◽

Local Immune Response ◽

Response Modulation ◽

Gene Expressions ◽

Expression Of Genes ◽

Age Related ◽

A Prospective Study ◽

Prospective Study Design

Abstract Background 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. Results 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. Conclusions 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.

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Lipidomic Profiling Reveals an Age-Related Deficiency of Skeletal Muscle Proresolving Mediators that Contributes to Maladaptive Tissue Remodeling

10.1101/2020.11.05.370056 ◽

2020 ◽

Author(s):

James F. Markworth ◽

Lemuel A. Brown ◽

Eunice Lim ◽

Jesus A. Castor-Macias ◽

Jacqueline Larouche ◽

...

Keyword(s):

Skeletal Muscle ◽

Immune Cell ◽

Tissue Remodeling ◽

Low Grade ◽

Resolvin D1 ◽

Minimal Impact ◽

Aged Mice ◽

Positive Effects ◽

Age Related ◽

Anti Inflammatory

AbstractChronic inflammation and deregulated acute immune cell responses to injury contribute to age-associated skeletal muscle dysfunction. Specialized pro-resolving mediators (SPMs) control inflammation and support myofiber regeneration in young mice, but their role in aging muscle remains unknown. Here we examined the effect of age on the mediator lipidome of skeletal muscle via LC-MS based lipidomic profiling and tested whether systemic administration of the SPM resolvin D1 (RvD1) could limit excessive inflammation and improve the regenerative capacity of aged muscle. Aged mice displayed chronic low-grade muscle inflammation prior to injury and this was associated with a basal deficiency of lipoxygenase (LOX) derived SPMs as well as anti-inflammatory cytochrome P450 (CYP) derived lipid epoxides. Following muscle damage, young and aged mice produced similar amounts of pro-inflammatory cyclooxygenase (COX) and 12-LOX metabolites, but aged mice mounted a markedly deficient SPM response. This was associated with heightened leukocyte recruitment, impaired myofiber regeneration, and delayed recovery of strength. Systemic treatment with RvD1 had minimal impact on excessive myeloid cell infiltration and defective myofiber regeneration in aged mice. Nevertheless, RvD1 treatment did suppress inflammatory cytokines, modulated muscle stem cells, limited maladaptive tissue remodeling, and improved recovery of specific muscle force. We conclude that aging results in a marked deficiency of local SPM biosynthesis within muscle and that immunoresolvents may be attractive novel therapeutics for the treatment of muscular injuries and associated pain in the elderly, due to positive effects on recovery of muscle function without the negative side effects on myofiber regeneration of traditional anti-inflammatory treatments.

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