Candidate rejuvenating factor GDF11 and tissue fibrosis: friend or foe?
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REVIEW
Candidate rejuvenating factor GDF11 and tissue fibrosis: friend or foe? Jan Frohlich & Manlio Vinciguerra
Received: 3 September 2020 / Accepted: 22 September 2020 # American Aging Association 2020
Abstract Growth differentiation factor 11 (GDF11 or bone morphogenetic protein 11, BMP11) belongs to the transforming growth factor-β superfamily and is closely related to other family member—myostatin (also known as GDF8). GDF11 was firstly identified in 2004 due to its ability to rejuvenate the function of multiple organs in old mice. However, in the past few years, the heralded rejuvenating effects of GDF11 have been seriously questioned by many studies that do not support the idea that restoring levels of GDF11 in aging improves overall organ structure and function. Moreover, with increasing controversies, several other studies described the involvement of GDF11 in fibrotic processes in various organ setups. This review paper focuses on the GDF11 and its pro- or anti-fibrotic actions in major organs and tissues, with the goal to summarize our knowledge on its emerging role in regulating the progression of fibrosis in different pathological conditions, and to guide upcoming research efforts.
Keywords Fibrosis . Growth differentiation factor 11 . GDF11 . BMP11 J. Frohlich : M. Vinciguerra (*) International Clinical Research Center, St. Anne’s University Hospital, Pekarska 53, 656 91 Brno, Czech Republic e-mail: [email protected] M. Vinciguerra Institute for Liver and Digestive Health, Division of Medicine, University College London (UCL), London, UK
Introduction Tissue damage repair is a fundamental process, critical for survival, allowing ordered replacement of dead or damaged cells. Even if this healing process is initially beneficial, it can become pathogenic under certain circumstances [1–3]. If unchecked, it can progress to considerable tissue remodeling and pathologic exchange of normal organ tissue architecture with formation of permanent scar tissue: fibrosis. Fibrosis is a characteristic feature of many chronic diseases that can end up in later stages with total organ failure of liver, lung, kidney, and heart [1, 4]. In the developed world, these fibrosisdriven diseases are a major cause of morbidity and mortality, accounting for 45% of all deaths [3]. The primary pathways associated with tissue injury and the development of fibrotic diseases are relatively well-studied in individual organs and are reviewed elsewhere [5–8]. Regardless of the fact that the causes of fibrotic diseases can be organ-specific and dissimilar, they all have common molecular mechanisms that is resulting in the uncontrolled and exacerbated production of extracellular matrix (ECM) components, and in the replacement of normal healthy tissue with nonfunctional fibrotic tissue [2, 9–12]. Deposited ECM components are mostly structural proteins (e.g., fibrous collagens I and III and elastin), adhesive proteins (e.g., laminin and fibronectin), and ground substance (e.g., glycosaminoglycans, such as hyaluronan and glycopro
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