The injury-induced transcription factor SOX9 alters the expression of LBR, HMGA2, and HIPK3 in human kidney

Am J Physiol Renal Physiol. 2022 Dec 1. doi: 10.1152/ajprenal.00196.2022. Online ahead of print.ABSTRACTInduction of SRY-box transcription factor 9 (SOX9) has been shown to occur in response to kidney injury in rodents, where SOX9-positive cells proliferate and regenerate the proximal tubules of injured kidneys. Additionally, SOX9-positive cells demonstrate a capacity to differentiate towards other nephron segments. Herein, we characterized the role of SOX9 in normal and injured human kidney. SOX9 expression was found to colocalize with a proportion of the so-called scattered tubular cells (STCs) in uninjured kidney, a cell population previously shown to be involved in kidney injury and regeneration. Following injury and in areas adjacent to inflammatory cell infiltrates, SOX9-positive cells were increased in number. Using primary tubular epithelial cells (PTECs) obtained from human kidney tissue, SOX9 expression was spontaneously induced in culture and further increased by TGFβ1, while it was suppressed by IFNγ. siRNA-mediated knockdown of SOX9 in PTECs followed by analysis of differential gene expression, immunohistochemical expression, and luciferase promoter assays, suggested lamin B receptor (LBR), high mobility group AT-hook 2 (HMGA2), and homeodomain interacting protein kinase 3 (HIPK3) as possible target genes of SOX9. Moreover, a kidney explant model was used to demonstrate that only SOX9-positive cells survive the massive injury associated with kidney ischemia and...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Source Type: research