
==== Front
Res Sq
ResearchSquare
Research Square
2693-5015
American Journal Experts

39184103
10.21203/rs.3.rs-4746078/v1
10.21203/rs.3.rs-4746078
preprint
1
Article
Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts
Rudman-Melnick Valeria
Vanhoutte Davy
Stowers Kaitlynn
Sargent Michelle
Adam Mike
Ma Qing
Perl Anne Karina T.
Miethke Alexander G.
Burg Ashley
Shi Tiffany
Hildeman David A.
Woodle E. Steve S.
Kofron J. Matthew
Devarajan Prasad
17 8 2024
rs.3.rs-4746078https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
https://www.researchsquare.com/article/rs-4746078/v1
nihpp-rs4746078v1.pdf
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.
==== Body
pmc
