Activin B, a new player in kidney fibrosis?^†

Abstract

Interest has been growing in the role of activin A in both acute and chronic kidney disease. The role of other activins, however, remains relatively unexplored. In a recent issue of The Journal of Pathology, an elegant study by Sun et al identified upregulation of INHBB, the subunit of activin B, in three different models of kidney fibrosis, as well as in human kidneys with fibrosis. This increase was shown to be mediated by upregulation of the transcription factor Sox9. Using overexpression and inhibition strategies, the importance of INHBB to kidney interstitial fibroblast activation and kidney fibrosis was clearly shown. Importantly, INHBB and Sox9 are not appreciably expressed in normal tissue. These studies lay important groundwork for the further investigation of activin B targeting as a potential therapeutic approach to attenuate kidney fibrosis.

The Role of Myofibroblasts in Physiological and Pathological Tissue Repair

“…Prominent examples include other members of the TGF-β family, PDGF, and fibroblast growth factor (FGF) family members, which are being investigated for their potential antifibrotic activity (Morikawa et al 2016;Lodyga and Hinz 2020). Activins and bone morphogenetic proteins (BMPs) are drawing increasing attention with regard to their role in regulating fibroblast activation and their value as therapeutic targets (Wietecha et al 2020;Duffy et al 2021;Krepinsky 2022). PDGF has long been studied as a key regulator of myofibroblast activation (Klinkhammer et al 2018) and was more recently found to coordinate a complex vascular niche in Dupuytren's disease (Layton et al 2022).…”

Paracrine activin B-NF-κB signaling shapes an inflammatory tumor microenvironment in gastric cancer via fibroblast reprogramming

“…Furthermore, overexpressing of activin B was identified in three different models of kidney fibrosis, as well as in human kidneys with fibrosis. Sox9-activin B provides a prospective entry point to surmount kidney fibrosis [ 9 , 10 ]. Nevertheless, there is still room for improvement in understanding its specific value in tumor research [ 11 ].…”