scholarly journals Increased vascular and uteroplacental matrix metalloproteinase-1 and -7 levels and collagen type I deposition in hypertension in pregnancy: role of TNF-α

2017 ◽  
Vol 313 (3) ◽  
pp. H491-H507 ◽  
Author(s):  
Wei Li ◽  
Ning Cui ◽  
Marc Q. Mazzuca ◽  
Karina M. Mata ◽  
Raouf A. Khalil
Keyword(s):  
Matrix Metalloproteinase ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Collagen Deposition ◽  
Related Disorder ◽  
Hypertension In Pregnancy ◽  
Tnf Α ◽  
Placental Ischemia ◽  
In Pregnancy

Preeclampsia is a pregnancy-related disorder manifested as maternal hypertension in pregnancy (HTN-Preg) and fetal growth restriction. Placental ischemia could be an initiating event that leads to abnormal vascular and uteroplacental remodeling in HTN-Preg; however, the molecular targets and intermediary mechanisms involved are unclear. We tested the hypothesis that placental ischemia could target vascular and uteroplacental matrix metalloproteinases (MMPs) through an inflammatory cytokine-mediated mechanism. MMP levels and distribution were measured in the aorta, uterus, and placenta of normal pregnant (Preg) rats and pregnant rats with reduced uterine perfusion pressure (RUPP). Maternal blood pressure was higher and the litter size and pup weight were lower in RUPP compared with Preg rats. Gelatin zymography showed prominent uterine MMP-2 and MMP-9 activity that was dependent on the amount of loaded protein. At saturating protein loading, both gelatin and casein zymography revealed two additional bands corresponding to MMP-1 and MMP-7 that were greater in the aorta, uterus, and placenta of RUPP compared with Preg rats. Western blots and immunohistochemistry confirmed increased MMP-1 and MMP-7 in the aorta, uterus, and placenta of RUPP versus Preg rats. The levels of MMP-1 and MMP-7 substrate collagen type I were greater in tissues of RUPP compared with Preg rats. In organ culture, TNF-α increased MMP-1 and MMP-7 in the aorta, uterus, and placenta of Preg rats, and a TNF-α antagonist prevented the increases in MMPs in tissues of RUPP rats. Thus, placental ischemia, possibly through TNF-α, increases vascular and uteroplacental MMP-1 and MMP-7, which, in turn, alter collagen deposition and cause inadequate tissue remodeling in HTN-Preg. Cytokine antagonists may reverse the increase in MMP-1 and MMP-7 expression/activity and, in turn, restore proper vascular and uteroplacental remodeling in HTN-Preg and preeclampsia. NEW & NOTEWORTHY The molecular mechanisms of preeclampsia are unclear, making it difficult to predict, prevent, or manage the pregnancy-associated disorder. This study showed that placental ischemia, possibly through the release of TNF-α, causes increases in the levels of matrix metalloproteinase (MMP)-1 and MMP-7, which could alter collagen deposition and cause inadequate uteroplacental and vascular remodeling in hypertension in pregnancy. The data suggest that targeting MMP-1 and MMP-7 and their upstream modulators, such as TNF-α, could provide a new approach in the management of hypertension in pregnancy and preeclampsia.

scholarly journals Antifibrotic cardioprotection of berberine via downregulating myocardial IGF-1 receptor-regulated MMP-2/MMP-9 expression in diabetic rats

2018 ◽  
Vol 315 (4) ◽  
pp. H802-H813 ◽  
Author(s):  
Guohua Li ◽  
Wenjuan Xing ◽  
Min Zhang ◽  
Fenghao Geng ◽  
Hongyan Yang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
High Glucose ◽  
Cardiac Fibrosis ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Diabetic Rats ◽  
Type I ◽  
Antifibrotic Effect

Diabetic cardiac fibrosis increases ventricular stiffness and facilitates the occurrence of diastolic dysfunction. Our previous studies have shown that berberine, a natural alkaloid, attenuates cardiac ischemia-reperfusion injury in diabetic rats. The aim of present study was to investigate the effects of long-term berberine treatment on cardiac remodeling in diabetic rats and the underlying mechanisms. Diabetic rats induced by low-dose streptozotocin injection combined with 8 wk of high-fat diet displayed significant cardiac matrix collagen deposition and dysfunction, whereas berberine administration (200 mg·kg−1·day−1, gavage 4 wk) significantly ameliorated cardiac fibrosis and dysfunction and reduced cardiac IGF-1 receptor (IGF-1R) expression in diabetic rats. Interestingly, IGF-1R expression was upregulated in cardiac fibroblasts isolated from diabetic hearts or cultured in high-glucose conditions (30 mM). High glucose treatment or IGF-1R overexpression increased matrix metalloproteinase (MMP)-2/MMP-9 expression, α-smooth muscle actin (α-SMA), and collagen type I expression in cardiac fibroblasts. In contrast, berberine treatment significantly inhibited IGF-1R expression and exerted an antifibrotic effect in high glucose-cultured cardiac fibroblasts, as manifested by decreased MMP-2/MMP-9, α-SMA, and collagen type I expression, whereas IGF-1R siRNA plus berberine treatment did not further enhance this antifibrotic effect compared with berberine treatment alone. Taken together, long-term berberine treatment ameliorates cardiac fibrosis and dysfunction by downregulating IGF-1R expression in cardiac fibroblasts and subsequently reducing MMP-2/MMP-9, α-SMA, and collagen type I expression in diabetic hearts. The findings suggest the therapeutic potential of berberine for diabetic cardiomyopathy associated with cardiac fibrosis. NEW & NOTEWORTHY Berberine downregulated IGF-1 receptor expression and matrix metalloproteinase-2/matrix metalloproteinase-9 levels in cardiac fibroblasts and thus inhibited fibroblast differentiation and collagen overproduction in diabetic hearts, suggesting a novel mechanism for antifibrotic cardioprotection of berberine in type 2 diabetes.

scholarly journals ACL transection influences mRNA levels for collagen type I and TNF-α in MCL scar

2002 ◽  
Vol 20 (3) ◽  
pp. 520-525 ◽  
Author(s):  
Tokifumi Majima ◽  
Ian K. Y. Lo ◽  
John A. Randle ◽  
Linda L. Marchuk ◽  
Nigel G. Shrive ◽  
...  
Keyword(s):  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Mrna Levels ◽  
Tnf Α ◽  
Acl Transection

scholarly journals Ηλεκτροφυσιολογικές και ηλεκτροανατομικές ιδιότητες του δεξιού κόλπου σε ασθενείς με εμμένουσα κολπική μαρμαρυγή

2015 ◽  
Author(s):  
Χρήστος Γουδής
Keyword(s):  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Tissue Inhibitor ◽  
Matrix Metalloproteinase 1

Σκοπός: Η κολπική μαρμαρυγή σχετίζεται με παθολογικό κολπικό υπόστρωμα. Στην παρούσα μελέτη διερευνήθηκε αν ασθενείς με μονήρη εμμένουσα κολπική μαρμαρυγή και ασθενείς με εμμένουσα κολπική μαρμαρυγή και μη ισχαιμική διατατική μυοκαρδιοπάθεια παρουσιάζουν διαφορές στις ηλεκτροφυσιολογικές και ηλεκτροανατομικές ιδιότητες του δεξιού κόλπου και στους βιοχημικούς δείκτες των μεταβολών του κολλαγόνου. Επίσης διερευνήθηκε η σχέση μεταξύ των δυναμικών του δεξιού κόλπου και των βιοχημικών δεικτών μεταβολών του κολλαγόνου στις δύο ομάδες.Μέθοδοι: Δέκα ασθενείς με εμμένουσα μονήρη κολπική μαρμαρυγή και οκτώ ασθενείς με εμμένουσα κολπική μαρμαρυγή και μη ισχαιμική διατατική μυοκαρδιοπάθεια συμπεριλήφθηκαν στη μελέτη. Προσδιορίστηκαν οι χρόνοι ανάνηψης του φλεβοκόμβου και οι δραστικές ανερέθιστες περίοδοι σε μήκη κύκλου 600ms, 500ms και 400ms, στο υψηλό και χαμηλό πλάγιο τοίχωμα δεξιού κόλπου, στον εγγύ στεφανιαίο κόλπο και δεξιό κολπικό ωτίο, και χαρτογραφήθηκε ο δεξιός κόλπος. Το αμινοτελικό προπεπτίδιο του κολλαγόνου τύπου Ι (serum N-terminal propeptide of collagen type I-PINP) και ο ιστικός αναστολέας της μεταλλοπρωτεϊνάσης-1 (tissue inhibitor of matrix metalloproteinases, TIMP-1), υπολογίστηκαν ως βιοχημικοί δείκτες σύνθεσης του κολλαγόνου τύπου Ι, ενώ το διασταυρούμενο καρβοξυτελικό τελοπεπτίδιο του κολλαγόνου τύπου Ι (cross-linked C-terminal telopeptide of collagen type I-CTx) και η μεταλλοπρωτεϊνάση-1 (matrix metalloproteinase-1, MMP-1) ως βιοχημικοί δείκτες αποδόμησης του κολλαγόνου τύπου Ι μεταξύ των δύο ομάδων.Αποτελέσματα: Δε διαπιστώθηκε σημαντική διαφορά στους χρόνους ανάνηψης του φλεβοκόμβου, στις δραστικές ανερέθιστες περιόδους στο υψηλό και χαμηλό πλάγιο τοίχωμα δεξιού κόλπου σε μήκη κύκλου 600ms, στις δραστικές ανερέθιστες περιόδους στον εγγύ στεφανιαίο κόλπο και το δεξιό κολπικό ωτίο, στο μέσο δυναμικό του δεξιού κόλπου και στους βιοχημικούς δείκτες μεταβολών του κολλαγόνου μεταξύ των δύο ομάδων. Σε ασθενείς με μονήρη εμμένουσα κολπική μαρμαρυγή τα επίπεδα ορού του TIMP-1 σχετίζονται με τα μέσα δυναμικά στο υψηλό πλάγιο και υψηλό οπίσθιο τοίχωμα του δεξιού κόλπου. Συμπέρασμα: Ασθενείς με μονήρη εμμένουσα κολπική μαρμαρυγή και ασθενείς με εμμένουσα κολπική μαρμαρυγή και μη ισχαιμκή διατατική μυοκαρδιοπάθεια παρουσιάζουν παρόμοιες μεταβολές στις ηλεκτροφυσιολογικές και ηλεκτροανατομικές ιδιότητες του δεξιού κόλπου, καθώς και παρόμοιες δομικές μεταβολές. Επιπλέον, ο βιοχημικος δείκτης της σύνθεσης κολλαγόνου TIMP-1 σχετίζεται με τα μέσα δυναμικά στο υψηλό πλάγιο και υψηλό οπίσθιο τοίχωμα του δεξιού κόλπου σε ασθενείς με μονήρη εμμένουσα κολπική μαρμαρυγή.

Epithelial-to-mesenchymal transition in fibrosis: Collagen type I expression is highly upregulated after EMT, but does not contribute to collagen deposition

2013 ◽  
Vol 319 (19) ◽  
pp. 3000-3009 ◽  
Author(s):  
Nynke A. Hosper ◽  
Paul P. van den Berg ◽  
Saskia de Rond ◽  
Eliane R. Popa ◽  
Martijn J. Wilmer ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I ◽  
Collagen Deposition ◽  
Mesenchymal Transition

Role of newly synthesized fibronectin in vascular smooth muscle cell migration on matrix-metalloproteinase-degraded collagen

2002 ◽  
Vol 30 (2) ◽  
pp. 102-107 ◽  
Author(s):  
E. Stringa ◽  
D. White ◽  
R. S. Tuan ◽  
V. Knauper ◽  
J. Gavrilovic
Keyword(s):  
Smooth Muscle ◽  
Matrix Metalloproteinase ◽  
Vascular Smooth Muscle ◽  
Collagen Type ◽  
Collagen Type I ◽  
Vascular Lesions ◽  
Type I ◽  
Smooth Muscle Cell Migration ◽  
Cellular Fibronectin

The migration of vascular smooth muscle cells (VSMC) is known to be a key process in the development of a number of vascular lesions, although the precise mechanisms involved have still to be elucidated. In the present study, the production of endogenous fibronectins by VSMC migrating across intact and matrix-metalloproteinase-degraded collagen type I has been explored. Cellular fibronectin seems to play a role in the enhanced migration seen when VSMC are exposed to degraded collagen and platelet-derived growth factor-BB. VSMC were found to synthesize both exon IIIA-containing fibronectin (which predominated) and exon IIIB-containing fibronectin. When these cells were exposed to substrates consisting of recombinant exon IIIA-or exon IIIB-containing fibronectin, rates of migration were not elevated above those seen with undegraded collagen. Endogenous fibronectin production may thus be necessary, but not sufficient, for VSMC migration over degraded collagenous substrates.

scholarly journals Combination Therapy With Polydeoxyribonucleotide and Pirfenidone Alleviates Symptoms of Acute Respiratory Distress Syndrome in Human Lung Epithelial A549 Cells

2020 ◽  
Vol 24 (Suppl 1) ◽  
pp. S56-64 ◽  
Author(s):  
Jae-Joon Hwang ◽  
Il-Gyu Ko ◽  
Jun-Jang Jin ◽  
Lakkyong Hwang ◽  
Sang-Hoon Kim ◽  
...  
Keyword(s):  
Growth Factor ◽  
Combination Therapy ◽  
Distress Syndrome ◽  
Collagen Type ◽  
Human Lung ◽  
A549 Cells ◽  
Collagen Type I ◽  
Type I ◽  
Tnf Α ◽  
Lung Epithelial

Purpose: Acute respiratory distress syndrome (ARDS) is characterized by its acute onset of symptoms such as bilateral pulmonary infiltrates, severe hypoxemia, and pulmonary edema. Many patients with ARDS survive in the acute phase, but then die from significant lung fibrosis.Methods: The effect of combination therapy with polydeoxyribonucleotide (PDRN) and pirfenidone on ARDS was investigated using human lung epithelial A549 cells. ARDS environment was induced by treatment with lipopolysaccharide and transforming growth factor (TGF)-β. Enzyme-linked immunoassay for connective tissue growth factor (CTGF) and hydroxyproline were conducted. Western blot for collagen type I, fibroblast growth factor (FGF), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was performed.Results: In this study, 8-μg/mL PDRN enhanced cell viability. Combination therapy with PDRN and pirfenidone and pirfenidone monotherapy suppressed expressions of CTGF and hydroxyproline and inhibited expressions of collagen type I and FGF. Combination therapy with PDRN and pirfenidone and PDRN monotherapy suppressed expression of TNF-α and IL-1β.Conclusions: The combination therapy with PDRN and pirfenidone exerted stronger therapeutic effect against lipopolysaccharide and TGF-β-induced ARDS environment compared to the PDRN monotherapy or pirfenidone monotherapy. The excellent therapeutic effect of combination therapy with PDRN and pirfenidone on ARDS was shown by promoting the rapid anti-inflammatory effect and inhibiting the fibrotic processes.

scholarly journals P045 Oncostatin M induces strong fibrotic and chemokine responses from primary colonic subepithelial myofibroblasts

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S154-S155
Author(s):  
G Kokkotis ◽  
G Tarapatzi ◽  
I Drygiannakis ◽  
E Filidou ◽  
L Kandilogiannakis ◽  
...  
Keyword(s):  
Collagen Type ◽  
Intestinal Inflammation ◽  
Collagen Type I ◽  
Oncostatin M ◽  
Type I ◽  
Dependent Manner ◽  
Chemokine Expression ◽  
Basal Expression ◽  
Tnf Α ◽  
Chronic Intestinal Inflammation

Abstract Background Oncostatin M (OSM) may play an important role in Inflammatory Bowel Disease (IBD) pathogenesis. Specifically, both OSM and its receptor are upregulated in inflamed colonic regions of IBD patients, and high OSM expression has been associated with failure to respond to anti-TNF therapy. Our aim was to investigate the effect of OSM in fibrotic factors and chemokine expression on primary colonic subepithelial myofibroblasts (SEMFs) from healthy individuals (HI). Methods Primary SEMFs were isolated from endoscopically-obtained colonic biopsies from HI. SEMFs were stimulated with 1, 10, or 100ng/ml OSM for 6 hours, with or without pre-stimulation with 5ng/ml IL-1α plus 50ng/ml TNF-α for 24h. Total RNA was collected and mRNA transcripts for collagen type I, type III, fibronectin, and the chemokines CCL2, CXCL9, CXCL10 and CXCL11 were measured by reverse transcription quantitative PCR. Results Unstimulated SEMFs had a basal expression of collagen type I, III, fibronectin, CCL2, CXCL9, CXCL10 and CXCL11. OSM stimulation augmented chemokine mRNA expression in a dose-dependent manner (Table 1) but had no effect on fibrotic factors expression. Pre-stimulation of myofibroblasts with TNF-α and IL-1α resulted in augmented expression of collagens I and III and fibronectin, in addition to further increases in chemokine expression in response to subsequent stimulation by OSM (Table 2). Conclusion Our results show that stimulation with OSM induces fibrotic and chemokine responses by SEMFs. Our findings further support the hypothesis that SEMFs may play a key role in regulating chronic intestinal inflammation and response to biological therapy.

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