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Review
. 2022 Oct 25;12(11):1557.
doi: 10.3390/biom12111557.

Insulin-like Growth Factor-2 (IGF-2) in Fibrosis

Yuhan Zhu  1 , Lin Chen  1 , Binyu Song  1 , Zhiwei Cui  1 , Guo Chen  1 , Zhou Yu  1 , Baoqiang Song  1
Affiliations
Review

Insulin-like Growth Factor-2 (IGF-2) in Fibrosis

Yuhan Zhu et al. Biomolecules. .

Abstract

The insulin family consists of insulin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2), their receptors (IR, IGF-1R and IGF-2R), and their binding proteins. All three ligands are involved in cell proliferation, apoptosis, protein synthesis and metabolism due to their homologous sequences and structural similarities. Insulin-like growth factor 2, a member of the insulin family, plays an important role in embryonic development, metabolic disorders, and tumorigenesis by combining with three receptors with different degrees of affinity. The main pathological feature of various fibrotic diseases is the excessive deposition of extracellular matrix (ECM) after tissue and organ damage, which eventually results in organic dysfunction because scar formation replaces tissue parenchyma. As a mitogenic factor, IGF-2 is overexpressed in many fibrotic diseases. It can promote the proliferation of fibroblasts significantly, as well as the production of ECM in a time- and dose-dependent manner. This review aims to describe the expression changes and fibrosis-promoting effects of IGF-2 in the skin, oral cavity, heart, lung, liver, and kidney fibrotic tissues.

Keywords: IGF-1R; IR; extracellular matrix (ECM); fibrosis; insulin-like growth factor 2 (IGF-2).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Molecular pathways of IGF-2 promotes organ fibrosis. By binding to IGF-1R, IR, and their heterodimers, IGF-2 actives the PI3K/Akt and JNK/c-jun signaling pathways to promote fibroblast proliferation, inhibit their apoptosis, and increase extracellular matrix (fibronectin and collagen) synthesis. IGF2 can also promote organ fibrosis by disrupting the TIMP/MMP balance and activating CaMKIIδ and calcineurin, as well as TGF-β signaling.
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This work was supported by grants from the National Natural Science Foundation of China (grant number 82002061 and 82072182).