Commentary: Role of estrogen receptor β in kidney disease

Abstract

Recent studies have shed light on the pivotal roles of estrogen in various pathophysiological processes related to kidney diseases. However, the precise mechanisms governing the estrogen actions remain enigmatic. The downstream impacts of estrogen primarily hinge on estrogen receptors (ERs), namely ERα (NR3A1) and ERβ (NR3A2). Building upon our previous finding that ERβ participates in subcutaneous adipose tissue browning in female mice, our recent study found that ERβ functions to protect kidney from progressive renal fibrosis by inactivating transforming growth factor-β (TGF-β)/Smad3 signaling. In the normal kidney, ERβ is highly expressed by proximal tubular epithelial cells but it is lost when kidney becomes fibrotic. In contrast, activation of ERβ inhibits kidney fibrosis. Mechanistically, we uncovered that ERβ can bind to Smad3, thereby transcriptionally downregulating Smad3 and inhibiting TGF-β1/Smad3-mediated renal fibrosis. Thus, ERβ is protective in renal fibrosis and may have therapeutic potential for chronic kidney disease.