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Review
. 2020 Nov 30;21(23):9138.
doi: 10.3390/ijms21239138.

TGF-β Pathway in Salivary Gland Fibrosis

Xianglan Zhang  1   2 , Jun Seop Yun  2   3   4 , Dawool Han  2   3 , Jong In Yook  2   3   4 , Hyun Sil Kim  2   3 , Eunae Sandra Cho  2   3   4
Affiliations
Review

TGF-β Pathway in Salivary Gland Fibrosis

Xianglan Zhang et al. Int J Mol Sci. .

Abstract

Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-β) pathway has a pivotal role in the pathogenesis of fibrosis in several organs, including the salivary glands. Among the TGF-β superfamily members, TGF-β1 and 2 are pro-fibrotic ligands, whereas TGF-β3 and some bone morphogenetic proteins (BMPs) are anti-fibrotic ligands. TGF-β1 is thought to be associated with the pro-fibrotic pathogenesis of sialadenitis, post-radiation salivary gland dysfunction, and Sjögren's syndrome. Potential therapeutic strategies that _target multiple levels in the TGF-β pathway are under preclinical and clinical research for fibrosis. Despite the anti-fibrotic effect of BMPs, their in vivo delivery poses a challenge in terms of adequate clinical efficacy. In this article, we will review the relevance of TGF-β signaling in salivary gland fibrosis and advances of potential therapeutic options in the field.

Keywords: BMP; Sjögren’s syndrome; TGF-β; drug delivery; fibrosis; salivary gland; sialadenitis.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Schematic image of TGF-β/SMAD and BMP/SMAD signaling pathway in fibrosis (upper left box, signal activation via TGF-β receptor and ligand attachment; orange and yellow circles/arrows, TGF-β ligands/signaling and BMP ligands/signaling, respectively). Abbreviations: TGF-β, transforming growth factor beta; BMP, bone morphogenetic protein; P, phosphorylation; I-SMAD, inhibitory SMAD; I, TGFβR1; II, TGFβR2.
Figure 2
Figure 2
Potential therapeutic _target sites in the TGF-β/BMP signaling pathway. (Orange and yellow circles/arrows, TGF-β ligands/signaling and BMP ligands/signaling, respectively). Abbreviations: TGF-β, transforming growth factor beta; BMP, bone morphogenetic protein; P, phosphorylation; I-SMAD, inhibitory SMAD; LAP, latency-associated proteins; LTBP, latent TGF-β binding protein; ECM, extracellular matrix; SLC, small latent complex; LLC, large latent complex.
Figure 3
Figure 3
Fibrosis in salivary gland diseases. Under hematoxylin and eosin stain (left) and Masson’s trichrome stain (right), fibrosis is presented as dense pink collagen bundles (green arrows) and dense blue collagen bundles (yellow arrows), respectively. (A,B). Fibrosis in sialadenitis of the submandibular gland (×200). (C,D). Fibrosis adjacent to lymphocytic aggregation (asterisks) in labial minor salivary glands diagnosed as Sjögren syndrome (×200).
See this image and copyright information in PMC

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