scholarly journals Calcitonin gene-related peptide down-regulates bleomycin-induced pulmonary fibrosis

2016 ◽  
Vol 94 (12) ◽  
pp. 1315-1324 ◽  
Author(s):  
Xian-Wei Li ◽  
Xiao-Hui Li ◽  
Jie Du ◽  
Dai Li ◽  
Yuan-Jian Li ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Calcitonin Gene Related Peptide ◽  
Collagen I ◽  
Lung Fibroblasts ◽  
Brdu Incorporation ◽  
Pulmonary Fibroblasts ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Collagen Iii ◽  
Tgf Β1

We have found that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis, and up-regulation of eIF3a induced by TGF-β1 is mediated via the ERK1/2 pathway. Whether ERK1/2 – eIF3a signal pathway is involved in calcitonin gene-related peptide (CGRP)-mediated pathogenesis of bleomycin-induced pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. Sensory CGRP depletion by capsaicin exacerbated bleomycin-induced pulmonary fibrosis in rats, as shown by a significant disturbed alveolar structure, marked thickening of the interalveolar septa and dense interstitial infiltration by inflammatory cells and fibroblasts, accompanied with increased expression of TGF-β1, eIF3a, phosphorylated ERK1/2, α-SMA, collagen I, and collagen III. Exogenous application of CGRP significantly inhibited TGF-β1-induced proliferation and differentiation of pulmonary fibroblasts concomitantly with decreased expression of eIF3a, phosphorylated ERK1/2, α-SMA, collagen I, and collagen III. These effects of CGRP were abolished in the presence of CGRP8-37. These results suggest that endogenous CGRP is related to the development of pulmonary fibrosis induced by bleomycin, and the inhibitory effect of CGRP on proliferation of lung fibroblasts involves the ERK1/2 – eIF3a signaling pathway.

scholarly journals Butyrate Prevents TGF-β1-Induced Alveolar Myofibroblast Differentiation and Modulates Energy Metabolism

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 258
Author(s):  
Hyo Yeong Lee ◽  
Somi Nam ◽  
Mi Jeong Kim ◽  
Su Jung Kim ◽  
Sung Hoon Back ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Mitochondrial Dynamics ◽  
Tca Cycle ◽  
Lung Fibroblasts ◽  
Myofibroblast Differentiation ◽  
Pulmonary Fibroblasts ◽  
Matrix Deposition ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a serious lung disease characterized by excessive collagen matrix deposition and extracellular remodeling. Signaling pathways mediated by fibrotic cytokine transforming growth factor β1 (TGF-β1) make important contributions to pulmonary fibrosis, but it remains unclear how TGF-β1 alters metabolism and modulates the activation and differentiation of pulmonary fibroblasts. We found that TGF-β1 lowers NADH and NADH/NAD levels, possibly due to changes in the TCA cycle, resulting in reductions in the ATP level and oxidative phosphorylation in pulmonary fibroblasts. In addition, we showed that butyrate (C4), a short chain fatty acid (SCFA), exhibits potent antifibrotic activity by inhibiting expression of fibrosis markers. Butyrate treatment inhibited mitochondrial elongation in TGF-β1-treated lung fibroblasts and increased the mitochondrial membrane potential (MMP). Consistent with the mitochondrial observations, butyrate significantly increased ADP, ATP, NADH, and NADH/NAD levels in TGF-β1-treated pulmonary fibroblasts. Collectively, our findings indicate that TGF-β1 induces changes in mitochondrial dynamics and energy metabolism during myofibroblast differentiation, and that these changes can be modulated by butyrate, which enhances mitochondrial function.

Monoklonale Antikörper gegen CGRP oder den CGRP-Rezeptor in der Migräneprophylaxe

2020 ◽  
Vol 39 (07/08) ◽  
pp. 490-494
Author(s):  
Borries Kukowski
Keyword(s):  
Monoklonale Antikörper ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

ZUSAMMENFASSUNGDie Charakterisierung von calcitonin gene-related peptide (CGRP) als Schlüsselmolekül in der Pathophysiologie der Migräne hat nicht nur unser Verständnis der Erkrankung, sondern auch die Entwicklung neuer Therapien vorangetrieben. Seit kurzem steht mit den monoklonalen Antikörpern gegen CGRP oder den CGRP-Rezeptor eine spezifische und hoch selektive Option für die medikamentöse Prophylaxe der episodischen und chronischen Migräne zur Verfügung, die in zahlreichen klinischen Studien ihre Überlegenheit gegenüber Placebo belegt hat. Hier werden Erfahrungen aus dem praktischen Behandlungsalltag zur kurz- und mittelfristigen Wirksamkeit und Verträglichkeit mitgeteilt und weitere Aspekte wie Therapiewechsel bei Non-Response, Verlauf nach Therapieende und die Frage des Wirkungsortes unter Einbeziehung bereits publizierter Daten angesprochen.

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