Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts

TL;DR

This study identifies Gucy1α1 as a specific marker for fibroblasts in multiple organs, offering a new way to target these cells in fibrosis.

Contribution

Gucy1α1 is shown as a novel, specific fibroblast marker across multiple organs and sexes.

Findings

Gucy1α1 levels increase in murine models of kidney disease and correlate with fibrosis markers.

Gucy1α1 labels fibroblasts in kidney, heart, and liver without off-target overlap.

GUCY1α1 is elevated in human fibrotic kidney and lung tissues.

Abstract

Fibrosis is a common outcome of numerous pathologies, including chronic kidney disease (CKD), a progressive renal function deterioration. Current approaches to target activated fibroblasts, key effector contributors to fibrotic tissue remodeling, lack specificity. Here, we report Gucy1α1 as a specific kidney fibroblast marker. Gucy1α1 levels significantly increased over the course of two clinically relevant murine CKD models and directly correlated with established fibrosis markers. Immunofluorescent (IF) imaging showed that Gucy1α1 comprehensively labelled cortical and medullary quiescent and activated fibroblasts in the control kidney and throughout injury progression, respectively. Unlike traditionally used markers platelet derived growth factor receptor beta (Pdgfrβ) and vimentin (Vim), Gucy1α1 did not overlap with off-target populations such as podocytes. Notably, Gucy1α1 labelled kidney fibroblasts in both male and female mice. Furthermore, we observed elevated GUCY1α1 expression in the human fibrotic kidney and lung. Studies in the murine models of cardiac and liver fibrosis revealed Gucy1α1 elevation in activated Pdgfrβ-, Vim- and alpha smooth muscle actin (αSma)-expressing fibroblasts paralleling injury progression and resolution. Overall, we demonstrate Gucy1α1 as an exclusive fibroblast marker in both sexes. Due to its multiorgan translational potential, GUCY1α1 might provide a novel promising strategy to specifically target and mechanistically examine fibroblasts.