Table 1.
TGF-β isoform specific differences.
| References | ||
|---|---|---|
| Structural differences | TGF-β3 shares 79% identity with TGF-β32 (see Fig. 1) | |
| TGF-β3 shares 76% identity with TGF- β1 (see Fig. 1) | ||
| TGF-β1 and TGF-β3 bind TβRII to initiate signal transduction | ||
| cascades whereas TGF-β2 requires binding of TβRIII prior to binding TβRII | ||
| The reported structures of TGF-β1 and TGF-β2 indicate that they adopt a rigid ‘closed’ structure. The structure for TGF-J33 indicates that its structure is flexible and capable of adopting either ‘open’ or ‘closed’ structures (see Fig. 2) | ||
| Differences observed in vitro | TGF-β1 induces migration of THP1 monocytes, whereas TGF-β3 does not | Unpublished |
| At low doses TGF-β1 induces collagen production by human dermal fibroblasts, whereas TGF-β3 does not | Unpublished | |
| TGF-β3 activates signal transduction pathways differently to TGF-β1, e.g., Smad | Unpublished | |
| TGF-β3 is a more potent inhibitor of DNA synthesis in human keratinocytes compared to TGF-β1 and TGF-β2 | [150] | |
| TGF-β3 is a more potent stimulator of neovascularisation compared to TGF-β1 and TGF-β2 as measured by the chicken chorio-allantoic membrane assay | [151] | |
| Whereas TGF-β1 and TGF-β2 have dose-dependent effects on the stimulation of granulocyte-macrophage colony stimulating factor from human bone marrow hematopoietic progenitor cells, TGF-β3 produced only an inhibitory effect and was more potent than other isoforms | [152] | |
| TGF-β3 is a more potent inhibitor of both interleukin-3-induced colony formation and IL-3 receptor expression compared to TGF-β1 | [153] | |
| TGF-β3 significantly increases cellular proliferation, whereas TGF-β1 induced precartilage condensation in posterfrontal suture-derived mesenchymal cells | [154] | |
| Tissue specific expression of TGF-β3 | TGF-β1, −β2 and −β3 are present in independent localised patterns during the process of secondary palate formation | [24] |
| TGF-β3 is the only isoform constitutively expressed in intact human epidermis | [70] | |
| TGF-β3 is an essential mediator of EMT in cardiac morphogenesis | [155,156] | |
| TGF-β3, but not TGF-β1 or TGF-β2, is up-regulated by milk stasis and induces apoptosis in mammary gland epithelium during involution | [157] | |
| TGF-β3 is a more potent regulator of functions associated with bone formation than TGF-β1 | [158] | |
| TGF-β3 mRNA expressed in most regions of the brain whereas TGF-β1 expression is induced following injury | [159,160] | |
| TGF-β3 but not TGF-β1 induces the expression of presenilin in post-mitotic neurons and astrocytes | [161] | |
| Transgenic phenotypes | TGF-β1 null animals display defects of hematopoiesis and vasculogenesis in development. | [19,20] |
| Those that survive to term present with a wasting syndrome and multi-organ failure due to inflammation after weaning | ||
| TGF-β2 null animals exhibit perinatal lethality as a result of developmental abnormalities | [21] | |
| TGF-β3 null animals die immediately after birth due to cleft palate and a failure to suckle | [22,23] | |
| Scarring and fibrosis | Exogenous addition of TGF-β3 to dermal wounds reduces scarring; neutralisation of TGF-β1 and TGF-β2 reduces scarring; exogenous addition of TGF-β1 and TGF-β2 has no effect on scarring | [31–33] |
| Neutralisation of TGF-β1 and TGF-β2 reduces adhesions; addition of exogenous TGF-β3 increases adhesions | [162] | |
| Exogenous addition of TGF-β3 to wounds changes the inflammatory and granulation cell profile | Unpublished | |
| TGF-β3 induces differential gene expression in wounds compared to TGF-β1 | Unpublished | |
| Progressive pulmonary fibrosis is mediated by TGF-β1 but not by TGF-β3 | [163] |