Progranulin:A promising biomarker and therapeutic target for fibrotic diseases

Progranulin(PGRN),a multifunctional growth factor-like protein expressed by a variety of cell types,serves an important function in the physiologic and pathologic processes of fibrotic diseases,including wound healing and the inflammatory response.PGRN was discovered to inhibit proinflammation effect by competing with tumor necrosis factor-alpha(TNF-a)binding to TNF receptors.Notably,excessive tissue repair in the development of inflammation causes tissue fibrosis.Previous investigations have indicated the significance of PGRN in regulating inflammatory responses.Recently,multiple studies have shown that PGRN was linked to fibrogenesis,and was considered to monitor the formation of fibrosis in multiple organs,including liver,cardiovascular,lung and skin.This paper is a comprehensive review summarizing our current knowledge of PGRN,from its discovery to the role in fibrosis.This is followed by an in-depth look at the characteristics of PGRN,consisting of its structure,basic function and intracellular signaling.Finally,we will discuss the potential of PGRN in the diagnosis and treatment of fibrosis.

Rapamycin in fibrotic diseases： beneficial or detrimental agent？

apamvcin was first isolated from a strain of Sreptomyces hygroscopicus in the early 1970s froma soil sample taken on Easter Island. Because the antiproliferative effects of rapamycin on yeast cell, as well as B and T lymphocytes, it was first identified as an antimicrobial agent with potent immunosuppressive activity and has been used in antirejection therapy.

Therapeutic potential for targeting Annexin A1 in fibrotic diseases

Annexin A1,a well-known endogenous anti-inflammatory mediator,plays a critical role in a variety of pathological processes.Fibrosis is described by a failure of tissue regeneration and contributes to the development of many diseases.Accumulating evidence supports that Annexin A1 participates in the progression of tissue fibrosis.However,the fundamental mechanisms by which Annexin A1 regulates fibrosis remain elusive,and even the functions of Annexin A1 in fibrotic diseases are still paradoxical.This review focuses on the roles of Annexin A1 in the development of fibrosis of lung,liver,heart,and other tissues,with emphasis on the therapy potential of Annexin A1 in fibrosis,and presents future research interests and directions in fibrotic diseases.

Understanding myofibroblast origin in the fibrotic lung

Idiopathic pulmonary fibrosis(IPF)is characterized by accumulation of myofibroblasts(MYFs)and extracellular matrix components,which leads to severe distortion and scarring of the gas exchange units of the lung,the alveoli,and ultimately respiratory failure.Fibrosis-associated MYFs are therefore widely regarded as the culprits that compromise the architectural makeup of the lung in fibrotic disease.During the past decade,the cellular source of MYFs has been intensely investigated.The rationale for such studies is that identifying the origin of these cells might help identify novel therapeutic targets and candidates to treat IPF patients.Recent advances in basic and translational research employing lineage tracing and multi-omics approaches have helped address the identity of MYF precursors,highlight the underlying heterogeneity,and to a less extent investigate MYF fate during fibrosis resolution.In this review,we discuss the current understanding of such important aspects of MYF biology as well as recent developments in the treatment of IPF.

Progress in drug delivery system for fibrosis therapy

Fibrosis is a necessary process in the progression of chronic disease to cirrhosis or even cancer,which is a serious disease threatening human health.Recent studies have shown that the early treatment of fibrosis is turning point and particularly important.Therefore,how to reverse fibrosis has become the focus and research hotspot in recent years.So far,the considerable progress has been made in the development of effective anti-fibrosis drugs and targeted drug delivery.Moreover,the existing research results will lay the foundation for more breakthrough delivery systems to achieve better anti-fibrosis effects.Herein,this review summaries anti-fibrosis delivery systems focused on three major organ fibrotic diseases such as liver,pulmonary,and renal fibrosis accompanied by the elaboration of relevant pathological mechanisms,which will provide inspiration and guidance for the design of fibrosis drugs and therapeutic systems in the future.