The Complexity of TGFβ/activin Signaling in Regeneration

Overview

Journal J Cell Commun Signal

Date 2021 Jan 22

PMID 33481173

Citations 8

Authors

Rene Fernando Abarca-Buis

Edna Ayerim Mandujano-Tinoco

Alejandro Cabrera-Wrooman

Edgar Krotzsch

Affiliations

Soon will be listed here.

Abstract

The role of transforming growth factor β TGFβ/activin signaling in wound repair and regeneration is highly conserved in the animal kingdom. Various studies have shown that TGF-β/activin signaling can either promote or inhibit different aspects of the regeneration process (i.e., proliferation, differentiation, and re-epithelialization). It has been demonstrated in several biological systems that some of the different cellular responses promoted by TGFβ/activin signaling depend on the activation of Smad-dependent or Smad-independent signal transduction pathways. In the context of regeneration and wound healing, it has been shown that the type of R-Smad stimulated determines the different effects that can be obtained. However, neither the possible roles of Smad-independent pathways nor the interaction of the TGFβ/activin pathway with other complex signaling networks involved in the regenerative process has been studied extensively. Here, we review the important aspects concerning the TGFβ/activin signaling pathway in the regeneration process. We discuss data regarding the role of TGF-β/activin in the most common animal regenerative models to demonstrate how this signaling promotes or inhibits regeneration, depending on the cellular context.

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References

Tang Y, Katuri V, Dillner A, Mishra B, Deng C, Mishra L . Disruption of transforming growth factor-beta signaling in ELF beta-spectrin-deficient mice. Science. 2003; 299(5606):574-7. DOI: 10.1126/science.1075994. View

Abarca-Buis R, Contreras-Figueroa M, Garciadiego-Cazares D, Krotzsch E . Control of fibrosis by TGFβ signalling modulation promotes redifferentiation during limited regeneration of mouse ear. Int J Dev Biol. 2020; 64(7-8-9):423-432. DOI: 10.1387/ijdb.190237ra. View

Whitby D, Ferguson M . Immunohistochemical localization of growth factors in fetal wound healing. Dev Biol. 1991; 147(1):207-15. DOI: 10.1016/s0012-1606(05)80018-1. View

Goumans M, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P, Ten Dijke P . Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J. 2002; 21(7):1743-53. PMC: 125949. DOI: 10.1093/emboj/21.7.1743. View

Bukowska J, Kopcewicz M, Kur-Piotrowska A, Szostek-Mioduchowska A, Walendzik K, Gawronska-Kozak B . Effect of TGFβ1, TGFβ3 and keratinocyte conditioned media on functional characteristics of dermal fibroblasts derived from reparative (Balb/c) and regenerative (Foxn1 deficient; nude) mouse models. Cell Tissue Res. 2018; 374(1):149-163. PMC: 6132647. DOI: 10.1007/s00441-018-2836-8. View

Thenappan A, Li Y, Kitisin K, Rashid A, Shetty K, Johnson L . Role of transforming growth factor beta signaling and expansion of progenitor cells in regenerating liver. Hepatology. 2010; 51(4):1373-82. PMC: 3001243. DOI: 10.1002/hep.23449. View

Mastellos D, DeAngelis R, Lambris J . Inducing and characterizing liver regeneration in mice: Reliable models, essential "readouts" and critical perspectives. Curr Protoc Mouse Biol. 2014; 3(3):141-170. PMC: 3886822. DOI: 10.1002/9780470942390.mo130087. View

Woodruff T . Regulation of cellular and system function by activin. Biochem Pharmacol. 1998; 55(7):953-63. DOI: 10.1016/s0006-2952(97)00477-2. View

McCusker C, Bryant S, Gardiner D . The axolotl limb blastema: cellular and molecular mechanisms driving blastema formation and limb regeneration in tetrapods. Regeneration (Oxf). 2016; 2(2):54-71. PMC: 4895312. DOI: 10.1002/reg2.32. View

10.

Alibardi L . Immunolocalization of FGF8/10 in the Apical Epidermal Peg and Blastema of the regenerating tail in lizard marks this apical growing area. Ann Anat. 2016; 206:14-20. DOI: 10.1016/j.aanat.2016.03.010. View

11.

Derynck R, Zhang Y . Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003; 425(6958):577-84. DOI: 10.1038/nature02006. View

12.

Janson D, Saintigny G, Zeypveld J, Mahe C, El Ghalbzouri A . TGF-β1 induces differentiation of papillary fibroblasts to reticular fibroblasts in monolayer culture but not in human skin equivalents. Eur J Dermatol. 2014; 24(3):342-8. DOI: 10.1684/ejd.2014.2312. View

13.

Mokalled M, Poss K . A Regeneration Toolkit. Dev Cell. 2018; 47(3):267-280. PMC: 6373444. DOI: 10.1016/j.devcel.2018.10.015. View

14.

Kragl M, Knapp D, Nacu E, Khattak S, Maden M, Epperlein H . Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature. 2009; 460(7251):60-5. DOI: 10.1038/nature08152. View

15.

Galliher A, Schiemann W . Src phosphorylates Tyr284 in TGF-beta type II receptor and regulates TGF-beta stimulation of p38 MAPK during breast cancer cell proliferation and invasion. Cancer Res. 2007; 67(8):3752-8. DOI: 10.1158/0008-5472.CAN-06-3851. View

16.

Kim S, Henen M, Hinck A . Structural biology of betaglycan and endoglin, membrane-bound co-receptors of the TGF-beta family. Exp Biol Med (Maywood). 2019; 244(17):1547-1558. PMC: 6920675. DOI: 10.1177/1535370219881160. View

17.

Feng X, Derynck R . Specificity and versatility in tgf-beta signaling through Smads. Annu Rev Cell Dev Biol. 2005; 21:659-93. DOI: 10.1146/annurev.cellbio.21.022404.142018. View

18.

Alibardi L . Histochemical, Biochemical and Cell Biological aspects of tail regeneration in lizard, an amniote model for studies on tissue regeneration. Prog Histochem Cytochem. 2014; 48(4):143-244. DOI: 10.1016/j.proghi.2013.12.001. View

19.

Taniguchi Y, Sugiura T, Tazaki A, Watanabe K, Mochii M . Spinal cord is required for proper regeneration of the tail in Xenopus tadpoles. Dev Growth Differ. 2008; 50(2):109-20. DOI: 10.1111/j.1440-169X.2007.00981.x. View

20.

Lee M, Pardoux C, Hall M, Lee P, Warburton D, Qing J . TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J. 2007; 26(17):3957-67. PMC: 1994119. DOI: 10.1038/sj.emboj.7601818. View