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Review
. 2023 Jan 6;13(1):119.
doi: 10.3390/biom13010119.

The Role of JAK/STAT Pathway in Fibrotic Diseases: Molecular and Cellular Mechanisms

Jia Liu  1   2 , Faping Wang  1   2 , Fengming Luo  1   2
Affiliations
Review

The Role of JAK/STAT Pathway in Fibrotic Diseases: Molecular and Cellular Mechanisms

Jia Liu et al. Biomolecules. .

Abstract

There are four members of the JAK family and seven of the STAT family in mammals. The JAK/STAT molecular pathway could be activated by broad hormones, cytokines, growth factors, and more. The JAK/STAT signaling pathway extensively mediates various biological processes such as cell proliferation, differentiation, migration, apoptosis, and immune regulation. JAK/STAT activation is closely related to growth and development, homeostasis, various solid tumors, inflammatory illness, and autoimmune diseases. Recently, with the deepening understanding of the JAK/STAT pathway, the relationship between JAK/STAT and the pathophysiology of fibrotic diseases was noticed, including the liver, renal, heart, bone marrow, and lung. JAK inhibitor has been approved for myelofibrosis, and subsequently, JAK/STAT may serve as a promising target for fibrosis in other organs. Therefore, this article reviews the roles and mechanisms of the JAK/STAT signaling pathway in fibrotic diseases.

Keywords: Janus kinases (JAK); cytokines; fibroblast; fibrosis; inhibitor; signal transducer and activator of transcription (STAT).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The structure of JAK. Schematic illustrating the four functional domains of JAK, FERM, SH2, pseudokinase, and Kinase. Figure prepared using information from various sources [20,21].
Figure 2
Figure 2
The structure of STAT. Schematic illustrating the conserved domain structure of STAT, including N-terminal domain (NTD), coiled-coil domain, DNA binding domain, transcriptional activation domain, SH2 domain, tyrosine activation domain (TAD). Figure prepared using information from various sources [20,26].
Figure 3
Figure 3
The activation of the JAK/STAT signaling pathway by cytokines. Schematic illustrating the preference of cytokines to bind JAK family. Figure prepared using information from various sources [21,34].
Figure 4
Figure 4
The role of JAK/STAT in renal fibrosis. Schematic illustrating the main JAK/STAT members may involve in renal fibrosis, primarily through ischemia reperfusion injury, inflammatory infiltration, and diabetic nephropathy to modulate renal fibrosis.
See this image and copyright information in PMC

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