Fig. 8: Effects of ERK1/2, SOX9 and Cyclin D1 gene knockdown on pathological changes and urinary protein secretion in Thy-1N rats. | Experimental & Molecular Medicine

Fig. 8: Effects of ERK1/2, SOX9 and Cyclin D1 gene knockdown on pathological changes and urinary protein secretion in Thy-1N rats.

From: Sublytic C5b-9 induces glomerular mesangial cell proliferation via ERK1/2-dependent SOX9 phosphorylation and acetylation by enhancing Cyclin D1 in rat Thy-1 nephritis

Fig. 8

a, b The protein levels of ERK1/2 (t-ERK1/2 and p-ERK1/2), SOX9 (SOX9 and p-SOX9), and Cyclin D1 (a) as well as SOX9 acetylation and its interaction with p-ERK1/2 (b) were measured at 3 h in the renal tissues of Thy-1N from different groups as indicated. c Renal ultrastructural changes on day 7 were examined by EM. d, e The changes in glomerular cell number in each group on day 7 were examined by H&E staining under LM. e The total contents of urinary protein (mg/24 h) on day 7 were detected. *p < 0.05, **p < 0.01 versus the NRS group; Δp < 0.05, ΔΔp < 0.01 versus the LV-shCTR + Thy-1N group. Data were represented as the means ± SD (n = 5 in vivo in each group). f A putative scheme for the molecular regulation of GMC proliferation triggered by sublytic C5b-9. In response to extracellular sublytic C5b-9 attack, ERK1/2 is phosphorylated and enters the GMC nucleus to form a complex with SOX9, leading to SOX9 phosphorylation at the Ser64 and Ser181 residues. Phosphorylation of SOX9 at these sites not only induces SOX9 nuclear localization but also enhances its acetylation by promoting the interaction of SOX9 with HATs, including KAT7, PCAF, and GCN5. In addition, ERK1/2-upregulated GCN5 is also implicated in SOX9 acetylation. Nuclear phosphorylated or acetylated SOX9 can be recruited to the Cyclin D1 promoter regions, causing its gene induction and GMC proliferation.

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