LAUSR

Glomerular disease is a major cause of acute kidney injury (AKI) and chronic kidney disease (CKD). The glomerular filtration barrier consists of the endothelium, the glomerular basement membrane (GBM), and podocytes. Damage to the glomeruli disrupts the filtration process, leading to either nephritic syndrome or nephrotic syndrome. Podocytes secrete type IV collagen, a key component of the GBM. However, whether podocytes secrete other collagens, such as collagen 1α1, and the role of collagen 1α1 in podocyte-associated glomerular diseases remain unclear. This study aims to investigate the role of collagen 1α1 in podocytes. We used Col1a1-GFPTg mice to identify the collagen-producing cell. Podocin-CreTg; Col1α1 floxed/floxed and Wt1CreERT2/+; Col1α1 floxed/floxed mice were employed to constitutively and conditionally knock out the Col1α1 gene in podocytes. Ischemia-reperfusion injury (IRI) was used as a model for AKI. We compared plasma levels of blood urea nitrogen (BUN), creatinine, and urine protein between littermate control mice and Col1α1 knockout mice under normal conditions and on day 7 after IRI. We discovered that podocytes are strong collagen-producing cells in both normal kidneys and IRI-affected kidneys. In Podocin-CreTg; Col1α1 floxed/floxed mice, knockout of the Col1α1 gene in podocytes did not result in abnormal plasma levels of BUN, creatinine, or increased proteinuria under normal conditions compared to littermate control. However, Col1α1 knockout in Wt1CreERT2/+; Col1α1 floxed/floxed mice led to significantly higher proteinuria compared to littermate controls. In the IRI model, higher proteinuria was observed at day 7 after IRI in Podocin-CreTg; Col1α1 floxed/floxed mice compared to littermate controls. In Podocin-CreTg; Col1α1 floxed/floxed mice, Col1α1 knockout does not lead to increased proteinuria under normal conditions but does so in the IRI model. In contrast, Col1α1 knockout in Wt1CreERT2/+; Col1α1 floxed/floxed mice is associated with higher proteinuria. This increase may be attributed to damage to the glomerular filtration barrier, potentially linked to podocyte injury or dysfunction. The mechanisms underlying this phenomenon in Wt1CreERT2/+; Col1α1floxed/floxed mice require further investigation.