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. 2023 Dec 28;300(2):105605. doi: 10.1016/j.jbc.2023.105605

Figure 9.

Figure 9

Hypothetical model describing regulation of prolidase expression by TGF-β1-Sp1-KLF6 axes. The schematic model shows the expression of prolidase under basal and TGF-β1 stimulated conditions. Left Panel- We propose that the basal expression of prolidase is primarily regulated at the transcriptional step by Sp1, since inhibition studies of Sp1 using Mith A abrogated prolidase expression. Right panel- We predict that TGF-β1 activates the SMAD pathway to induce the expression of KLF6. Higher levels of KLF6 enhance Sp1-mediated PEPD promoter activity. The cooperative interaction of KLF6 and Sp1 at the overlapping binding sites within the PEPD promoter upregulates prolidase expression. Inhibition of TGF-β1 signaling by an SMAD3 inhibitor suppresses KLF6/Sp1-mediated activation of PEPD promoter-driven transcription. Finally, upregulation of prolidase during TGF-β1 signaling catalyzes the rate-limiting step in collagen biosynthesis to produce higher levels of collagen such as Col1A1. Collectively, this hypothetical model describes a mechanism for the molecular regulation of prolidase at the transcriptional level.