Fibrosis: Sirtuins at the checkpoints of myofibroblast differentiation and profibrotic activity

Zullo, Alberto; Mancini, Francesco Paolo; Schleip, Robert; Wearing, Scott; Klingler, Werner

doi:10.1111/wrr.12943

Cited by 9 publications

(7 citation statements)

References 179 publications

(308 reference statements)

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“…On the contrary, scientific discoveries have confirmed that early stage of fibrotic diseases is reversible, the effective measures contain removal or elimination of the causative agent. But it seems impossible to timely occurrence reversible and appropriately wound-healing, used to avoid complications ( 6 , 7 ). Despite decades of research on fibrotic diseases, few effective and clinical anti-fibrotic drugs have been discovered yet ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Shan

et al. 2022

Front. Immunol.

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G protein-coupled receptor kinase 2 (GRK2), an important subtype of GRKs, specifically phosphorylates agonist-activated G protein-coupled receptors (GPCRs). Besides, current research confirms that it participates in multiple regulation of diverse cells via a non-phosphorylated pathway, including interacting with various non-receptor substrates and binding partners. Fibrosis is a common pathophysiological phenomenon in the repair process of many tissues due to various pathogenic factors such as inflammation, injury, drugs, etc. The characteristics of fibrosis are the activation of fibroblasts leading to myofibroblast proliferation and differentiation, subsequent aggerate excessive deposition of extracellular matrix (ECM). Then, a positive feedback loop is occurred between tissue stiffness caused by ECM and fibroblasts, ultimately resulting in distortion of organ architecture and function. At present, GRK2, which has been described as a multifunctional protein, regulates copious signaling pathways under pathophysiological conditions correlated with fibrotic diseases. Along with GRK2-mediated regulation, there are diverse effects on the growth and apoptosis of different cells, inflammatory response and deposition of ECM, which are essential in organ fibrosis progression. This review is to highlight the relationship between GRK2 and fibrotic diseases based on recent research. It is becoming more convincing that GRK2 could be considered as a potential therapeutic target in many fibrotic diseases.

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Section: Introductionmentioning

confidence: 99%

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Shan

et al. 2022

Front. Immunol.

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“…We will further elaborate on the consequences of lost mechanical integrity in conditions of skin injury, with a spotlight on fibroblasts and myofibroblasts. Other aspects of fibroblast-to-myofibroblast regulation 9 and other fibroblast activities, such as inflammatory actions are discussed elsewhere. 10 After a brief survey of major fibrillar ECM protein components in the healthy skin, we will address the origins and heterogeneity of skin fibroblasts and how they respond to various ECM cues.…”

Section: Introductionmentioning

confidence: 99%

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

Sawant

Hinz

Schönborn

et al. 2021

Wound Repair Regeneration

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Our skin is continuously exposed to mechanical challenge, including shear, stretch, and compression. The extracellular matrix of the dermis is perfectly suited to resist these challenges and maintain integrity of normal skin even upon large strains. Fibroblasts are the key cells that interpret mechanical and chemical cues in their environment to turnover matrix and maintain homeostasis in the skin of healthy adults. Upon tissue injury, fibroblasts and an exclusive selection of other cells become activated into myofibroblasts with the task to restore skin integrity by forming structurally imperfect but mechanically stable scar tissue. Failure of myofibroblasts to terminate their actions after successful repair or upon chronic inflammation results in dysregulated myofibroblast activities which can lead to hypertrophic scarring and/or skin fibrosis. After providing an overview on the major fibrillar matrix components in normal skin, we will interrogate the various origins of fibroblasts and myofibroblasts in the skin. We then examine the role of the matrix as signaling hub and how fibroblasts respond to mechanical matrix cues to restore order in the confusing environment of a healing wound.

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“…6). This was surprising, as it would be expected that a change in tissue structure would take more time [51]. Although this case is not representative, it provides interesting food for thought regarding the mechanisms behind this improvement in morphology.…”

Section: Discussionmentioning

confidence: 88%

Influence of sports activity, thoracolumbar fascia morphology and myofascial release treatment on lumbar microcirculation: a randomized, placebo-controlled trial

Brandl

Egner

Reer

et al. 2022

Preprint

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Inflammatory processes in the thoracolumbar fascia lead to thickening, compaction, and fibrosis and are thought to contribute to the development of nonspecific low back pain (nLBP). The blood circulation of fascial tissue may play a critical role in this process, as it may promote hypoxia-induced inflammation. This study examined the influence of thoracolumbar fascia morphology (TLFM), sports activity (SA), body mass index (BMI), pain, and a set of myofascial release (MFR) techniques on blood flow data (BFD) of lumbar myofascial tissue. This study was a single-blind, randomized, placebo-controlled trial. Thirty pain-free subjects (40.5 ± 14.1 years) were randomly assigned to two groups treated with MFR or a placebo intervention. Correlations between pain, SA, BMI, and TLFM were calculated at baseline. The effects of TFLM and MFR on BFD were determined. There were strong correlations between pain (r = -0.648), SA (d = 0.681), BMI (r = -0.798), and TLFM. Blood flow was significantly different between disorganized and organized TLFM (p < 0.0001). The MFR group had a significant increase in blood flow after treatment (31.6%) and at follow-up (48.7%) compared with the placebo group. Circulatory restrictions caused by disorganized TFLM could lead to hypoxia-induced inflammation, which likely results in pain and impaired proprioceptive function and contributes to the development of nLBP. The deformation and altered morphology associated with dysfunction of blood vessels and free nerve endings could be positively affected by the intervention in this study.

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Fibrosis: Sirtuins at the checkpoints of myofibroblast differentiation and profibrotic activity

Cited by 9 publications

References 179 publications

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

Influence of sports activity, thoracolumbar fascia morphology and myofascial release treatment on lumbar microcirculation: a randomized, placebo-controlled trial

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