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Review
. 2021 Feb 25:8:628519.
doi: 10.3389/fmed.2021.628519. eCollection 2021.

TGF-β1 Signaling: Immune Dynamics of Chronic Kidney Diseases

Philip Chiu-Tsun Tang  1 , Alex Siu-Wing Chan  2 , Cai-Bin Zhang  1 , Cristina Alexandra García Córdoba  1 , Ying-Ying Zhang  3 , Ka-Fai To  1 , Kam-Tong Leung  4 , Hui-Yao Lan  5   6 , Patrick Ming-Kuen Tang  1
Affiliations
Review

TGF-β1 Signaling: Immune Dynamics of Chronic Kidney Diseases

Philip Chiu-Tsun Tang et al. Front Med (Lausanne). .

Abstract

Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide, imposing a great burden on the healthcare system. Regrettably, effective CKD therapeutic strategies are yet available due to their elusive pathogenic mechanisms. CKD is featured by progressive inflammation and fibrosis associated with immune cell dysfunction, leading to the formation of an inflammatory microenvironment, which ultimately exacerbating renal fibrosis. Transforming growth factor β1 (TGF-β1) is an indispensable immunoregulator promoting CKD progression by controlling the activation, proliferation, and apoptosis of immunocytes via both canonical and non-canonical pathways. More importantly, recent studies have uncovered a new mechanism of TGF-β1 for de novo generation of myofibroblast via macrophage-myofibroblast transition (MMT). This review will update the versatile roles of TGF-β signaling in the dynamics of renal immunity, a better understanding may facilitate the discovery of novel therapeutic strategies against CKD.

Keywords: chronic kidney disease; immunity; kidney fibrosis; renal inflammation; transforming growth factor β.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
TGF-β1 in immune cell mediate CKD progression. TGF-β1 modulates immune cell activity in the progression of chronic kidney disease (CKD). After kidney injury, TGF-β1 is released by kidney cells to aid the resolution of inflammation. However, persistent TGF-β1 signaling activation would promote a chronic inflammation state via amplification of inflammatory responses. Notably, chronic TGF-β1 signaling activation would further transdifferentiate macrophage into myofibroblast to produce excessive extracellular matrix molecules (Collagen I and fibronectin), thus eventually lead to the pathogenesis of CKD.
Figure 2
Figure 2
Role of TGF-β1 in unresolved inflammation. TGF-β1 activation promotes innate immune cells accumulation (neutrophil, macrophage, and dendritic cell) at the inflammatory site, which in-turn further activate adaptive immune cells (B and T cells) and dendritic cells to amplify the inflammatory responses in chronic inflamed kidney.
See this image and copyright information in PMC

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