SAT-247 - Effects of FSTL3 Deletion on Renal Structure and Function in Mice

TGFb ligand signalling plays crucial roles in kidney development and function. Among this group of pleiotropic ligands, growth and differentiation factor 11 (GDF11) is important in the development of the kidney by regulating gene expression from the metanephric mesenchyme. One of the known endogenous regulators of GDF11, and the related ligand activin, is follistatin like 3 (FSTL3). FSTL3 is increased in renal dysfunction highlighting the requirement of a balanced regulation of the TGFb ligand signalling system for renal health. The FSTL3 KO mouse is therefore a model in which the role of increased activin and GDF11 action on kidney structure and function can be interrogated. Using kidney samples from wild-type (WT) and FSTL3 knock out (KO) mice, we investigated the effect of FSTL3 deletion on kidney structure and organ maintenance. We found an altered structure of the renal corpuscles and tubules, within the cortex and medulla respectively. Masson trichrome staining demonstrated that there are clear differences in extracellular matrix deposition in the absence of FSTL3. In terms of signalling pathways, both SMAD2/3 and AKT dependent signalling was upregulated in the FSTL3 KO mice, which might be important in promoting increased cellular proliferation seen in FSTL3 KO kidneys. It was also found that markers involved in angiogenesis and proliferation were altered between WT and FSTL3 KO, which will have feedback effects on kidney structure and function. Taken together, our data demonstrates a novel role for FSTL3 in the regulation of renal structure, involving the alteration of renal proliferation and angiogenesis. These findings may help to better understand the role of FSTL3 and TGFb signalling in various kidney diseases.

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