Self-eating: friend or foe? The emerging role of autophagy in fibrotic diseases

Liu, Runping; Wu, Jianzhi; Li, Xiaojiaoyang

doi:10.7150/thno.47826

Cited by 40 publications

(35 citation statements)

References 183 publications

(196 reference statements)

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“…As stated before, the induction of lung brosis by CeO 2 NP is in accordance with experimental data from literature, exploring the consequences of pulmonary administration of CeO 2 NP but also chemically different NP, such as Silica (Si) NP (1,(5)(6)(7)(8)(9)32). When it comes to the role of autophagy in this particle-induced lung brotic process, the literature is far less clear (33), as it contains both references that autophagy is protective (11,13,34,35), and also that it can be deleterious (36)(37)(38)(39). Using the same mice model, Jessop and colleagues demonstrated a greater silica-induced lung brosis, together with enhanced in ammation in Atg5 +/mice as compared to their WT littermates (40).…”

Section: Discussionsupporting

confidence: 57%

Deficient macrophage autophagy protects mice from Cerium Oxide nanoparticle-induced lung fibrosis

Annangi

Bruniaux

et al. 2021

Preprint

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Background: Cerium (Ce) is a rare earth element, rapidly oxidizing to form CeO2, and currently used in numerous commercial applications, especially as nanoparticles (NP). The potential health effects of Ce remain uncertain, but literature indicates the development of rare earth pneumoconiosis accompanied with granuloma formation, interstitial fibrosis and inflammation. The exact underlying mechanisms are not yet completely understood, and we propose that autophagy could be an interesting target to study, particularly in macrophages. Therefore, the objective of our study was to investigate the role of macrophagic autophagy after pulmonary exposure to CeO2 NP in mice. Mice lacking the early autophagy gene Atg5 in their myeloid lineage and their wildtype counterparts were exposed to CeO2 NP by single oropharyngeal administration and sacrificed up to one month after. At that time, lung remodeling was thoroughly characterized (inflammatory cells infiltration, expression of fibrotic markers such as αSMA, TGFβ1, total and type I and III collagen deposition), as well as macrophage infiltration (quantification and M1/M2 phenotype). Results: Such pulmonary exposure to CeO2 NP induces a progressive and dose-dependent lung fibrosis in the bronchiolar and alveolar walls, together with the activation of autophagy. Blockage of macrophagic autophagy protects from alveolar but not bronchiolar fibrosis, via the modulation of macrophage polarization towards M2 phenotype. Conclusion: In conclusion, our findings bring novel insight on the role of macrophagic autophagy in lung fibrogenesis, and add to the current awareness of pulmonary macrophages as important players in the disease.

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Section: Discussionsupporting

confidence: 57%

Deficient macrophage autophagy protects mice from Cerium Oxide nanoparticle-induced lung fibrosis

Annangi

Bruniaux

et al. 2021

Preprint

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“…With protracted damage, fibrosis may progress toward excessive scarring and organ failure. Fibrosis occurs in most human organs including the liver, lung, heart, and kidney, and is crucial for the progression of most chronic diseases [ 1 ]. In addition, fibrotic scar formation through fibroblasts and pericytes may also contribute to abnormal functioning and lack of recovery of the blood–brain barrier (BBB) during acute and chronic pathologies of the central nervous system such as traumatic spinal cord injury and multiple sclerosis [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis

Pesce

Bramanti

Iapichino³

et al. 2020

Molecules

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Liver fibrosis is defined as excessive extracellular matrix deposition in the hepatic parenchyma as a consequence of complex interactions among matrix-producing hepatic stellate cells (HSCs) and liver-resident and infiltrating cells. In addition to the liver, the process of fibrosis may represent end-stage disease of several diseases including kidneys, lungs, spleens, heart, muscles and at certain extent, the central nervous system and the peripheral nerves. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development. The aim of the present study was to test the efficacy of a new drug combination for the treatment of hepatic fibrosis in order to provide a proof-of-concept for the use of therapeutic agents in clinical practice. For this purpose, we have studied the effects of the PDGF inhibitor imatinib and the angiogenesis inhibitor sorafenib, administered alone or in combination, in reducing the progression of the fibrogenetic process in a pre-clinical model of liver damage induced in mice by repeated administration of Concanavalin A (ConA), resembling long-tern autoimmune hepatitis. Our results suggest that treatments with imatinib and sorafenib can modulate potently and, in a superimposable fashion, the fibrinogenic process when administered alone. However, and in agreement with the computational data presently generated, they only exert partial overlapping antifibrotic effects in modulating the main pathways involved in the process of liver fibrosis, without significant additive or synergist effects, when administered in combination.

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“…Therefore, ageing and profibrotic gene inheritance serve as additional "self-contained spontaneous stressors" that can impair the cellular homeostatic autophagic machinery, which is indispensable for cardiac tissue repair and proteostasis rebalancing [49][50][51][52]. Regulation of autophagy pathways are strongly implicated in liver, lung, heart, kidney and cystic fibrosis, which suggests that autophagy is a potential target for the treatment of chronic multiorgan fibrotic diseases involving aberrant extracellular remodeling [53]. The divergent homeostatic pathways converge to counter cellular stress or clear the stressor by intersecting and coordinating with precision, therefore, the intersection points, interacting partners and regulatory nodes are under extensive research.…”

Section: Abortive Cellular Homeostasis Rebalancing In Cardiac Fibrosimentioning

confidence: 99%

The Cellular Stress Response Interactome and Extracellular Matrix Cross-Talk during Fibrosis: A Stressed Extra-Matrix Affair

Sharma¹,

Kaushal²,

Rawat³

et al. 2021

Extracellular Matrix - Developments and Therapeutics

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Diverse internal and external pathologic stimuli can trigger cellular stress response pathways (CSRPs) that are usually counteracted by intrinsic homeostatic machinery, which responds to stress by initiating complex signaling mechanisms to eliminate either the stressor or the damaged cells. There is growing evidence that CSRPs can have context-dependent homeostatic or pathologic functions that may result in tissue fibrosis under persistence of stress. CSRPs can drive intercellular communications through exosomes (trafficking and secretory pathway determinants) secreted in response to stress-induced proteostasis rebalancing. The injured tissue environment upon sensing the stress turns on a precisely orchestrated network of immune responses by regulating cytokine-chemokine production, recruitment of immune cells, and modulating fibrogenic niche and extracellular matrix (ECM) cross-talk during fibrotic pathologies like cardiac fibrosis, liver fibrosis, laryngotracheal stenosis, systemic scleroderma, interstitial lung disease and inflammatory bowel disease. Immunostimulatory RNAs (like double stranded RNAs) generated through deregulated RNA processing pathways along with RNA binding proteins (RBPs) of RNA helicase (RNA sensors) family are emerging as important components of immune response pathways during sterile inflammation. The paradigm-shift in RNA metabolism associated interactome has begun to offer new therapeutic windows by unravelling the novel RBPs and splicing factors in context of developmental and fibrotic pathways. We would like to review emerging regulatory nodes and their interaction with CSRPs, and tissue remodeling with major focus on cardiac fibrosis, and inflammatory responses underlying upper airway fibrosis.

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Self-eating: friend or foe? The emerging role of autophagy in fibrotic diseases

Cited by 40 publications

References 183 publications

Deficient macrophage autophagy protects mice from Cerium Oxide nanoparticle-induced lung fibrosis

Deficient macrophage autophagy protects mice from Cerium Oxide nanoparticle-induced lung fibrosis

Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis

The Cellular Stress Response Interactome and Extracellular Matrix Cross-Talk during Fibrosis: A Stressed Extra-Matrix Affair

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