The Open Rheumatology Journal

ISSN: 1874-3129 ― Volume 13, 2019

Mediators of Fibrosis

Maria Trojanowska*, §
Arthritis Center, Boston University Medical Center, 72 East Concord St, E-5 Boston, MA 02118, USA

Article Information

Identifiers and Pagination:

Year: 2012
Volume: 6
Issue: Suppl 1
First Page: 70
Last Page: 71
Publisher Id: TORJ-6-70
DOI: 10.2174/1874312901206010070

Article History:

Electronic publication date: 15/6/2012
Collection year: 2012

Article Metrics:

CrossRef Citations:

Total Statistics:

Full-Text HTML Views: 742
Abstract HTML Views: 673
PDF Downloads: 198
Total Views/Downloads: 1613

Unique Statistics:

Full-Text HTML Views: 468
Abstract HTML Views: 435
PDF Downloads: 137
Total Views/Downloads: 1040
Geographical View

© Maria Trojanowska; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Arthritis Center, Boston University Medical Center, 72 East Concord St, E-5 Boston, MA 02118, USA; Tel: 617-638-4318; Fax: 617-638-5226; E-mail:§ Guest Editor

Progressive, uncontrolled deposition of extracellular matrix proteins leading to scar tissue formation and organ failure represents a final common pathway of tissue response to chronic injury. The nature of the insult varies between organs and tissues and may include viral infections or toxic agents, but in most cases the specific trigger remains unknown. Extensive research on the mechanisms of fibrosis has greatly contributed to a better understanding of the pathological mechanisms involved in this process. While we are learning more about the pathways that contribute to fibrosis, it would be important to integrate this new information with the large body of existing knowledge on the profibrotic mediators, especially Transforming Growth factor β (TGFβ). TGFβ is one of the most potent inducers of extracellular matrix and has long been considered to be a principal mediator of fibrosis. In addition to activation of both Smad-dependent and Smad-independent signaling pathways, TGFβ is involved in an extensive crosstalk with multiple other cellular pathways. Better understanding of the regulatory networks governing the fibrotic response at the cellular level will help to define the key regulatory molecules and advance the design of logical therapeutic targets. This series of articles will highlight some of the new developments in the field of fibrotic mediators.

There is a renewed interest in immune mediators and their influence on the process of fibrosis. In their article, Lafyatis and Farina provide an overview of the innate immune sensors and describe how they are linked to the inflammatory and profibrotic pathways. In a related article Artlett further explores the role of the NLRP3 inflammasome in inducing inflammatory and fibrotic responses.

Excessive production of Reactive Oxygen Species (ROS) leading to oxidative stress plays a major role in impairment of physiological processes. Oxidative stress has been associated with various diseases, including organ fibrosis, as well as aging. The article by Gabrielli provides an in depth discussion on the role of ROS in the pathogenesis of scleroderma. Recent studies using ROS-induced mouse models of scleroderma have revealed an important role of Notch-activation in the development of organ fibrosis. The Notch signaling pathway regulates the differentiation process in many cell types and its dysregulation is associated with several diseases, including cancer. More recently activation of Notch signaling has been linked to fibrotic diseases. Kavian and colleagues present new insights into the mechanisms of Notch signaling in fibrosis.

Peroxisome proliferator activated receptor β (PPAR-β) is a well-known regulator of lipid metabolism and glucose homeostasis. In their review article Wei and colleagues summarize a large body of evidence that links aberrant expression of PPAR-γ to the process of fibrosis. PPAR-γ agonists are currently used to treat type 2 diabetes and novel PPAR-γ based drugs are being actively developed; in the future these or similar compounds may also be helpful in treating scleroderma and other fibrotic conditions. Another attractive therapeutic target for scleroderma lung disease is caveolin-1. Caveolin-1 is a master regulator of several signaling cascades and its deficiency in pulmonary fibrosis affects multiple pathways in collagen producing cells. Tourkina and Hoffman discuss a novel strategy to restore caveolin-1 function that may be utilized to treat patients with pulmonary fibrosis. There are also accumulating data that bioactive sphingolipids play an important role in regulating inflammation and other aspects of the fibrotic process in numerous organ systems. Shea and Tager review the role of sphingolipids in organ fibrosis and discuss the prospect of targeting components of the spingolipid signaling pathway for treatment of fibrotic diseases.

Although, only discovered in the past decade, microRNAs are now recognized as critical regulators of post-transcriptional gene expression across various biological processes. The human genome is now predicted to encode nearly 1,000 miRNAs that likely regulate at least one third of all human transcripts. In their article, Vettori and colleagues provide a comprehensive overview of those microRNAs that are involved in regulating profibrotic pathways. The authors also discuss the pros and cons of the microRNA-based therapies.

Another area of active research involves various extracellular signaling molecules that affect fibrosis through novel mechanisms. Two of the articles describe the properties of such profibrotic molecules: Veraldi and Feghali-Bostwick discuss the role of Insulin-like growth factor binding protein -3 and -5 (IGFBP-3 and -5), while Trombetta-eSilva and Bradshaw summarize the potential profibrotic function of Secreted protein acidic and rich in cysteine (SPARC).

Although TGFβ represents an attractive theraputic target, its pleiotropic nature and complexity of signaling present significant challenges in considering anti-TGFβ therapies. Nakerakanti and Trojanowska review the specific components of the TGFβ signaling cascade that are altered in human fibrotic diseases. Targeting those dysregulated downstream signaling molecules may provide alternative strategies to ameliorate excessive TGFβ signaling.

Activated fibroblasts or myofibroblasts are the final effector cells responsible for excessive matrix deposition. As pointed out in the review article by Leask, dysregulation of multiple pathways contribute to this condition. It is clear that targeting a single pathway may not be effective therapeutically and that a combination therapy, as currently used to treat cancer or cardiovascular diseases, would be more beneficial. Although there is no shortage of potential therapeutic targets, currently there is no proven effective treatment for organ fibrosis. Since many pathological pathways relevant to the progression of fibrosis are also shared by other disorders, there is hope that effective treatments will be available in the near future.


"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."

Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."

Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."

Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."

Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."

Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."

Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."

Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."

J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."

Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."

Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."

Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."

Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."

Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."

M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."

Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."

Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."

Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."

Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."

Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."

Jih Ru Hwu
(National Central University, Taiwan)

SCImago Journal Ranking

SCImago Journal & Country Rank

Browse Contents

Webmaster Contact:
Copyright © 2019 Bentham Open