Fig. 9: TGFβ1 induces TXNDC5 expression in HPF through ER stress-dependent ATF6 activation. | Nature Communications

Fig. 9: TGFβ1 induces TXNDC5 expression in HPF through ER stress-dependent ATF6 activation.

From: Fibroblast-enriched endoplasmic reticulum protein TXNDC5 promotes pulmonary fibrosis by augmenting TGFβ signaling through TGFBR1 stabilization

Fig. 9

a TGFβ1 treatment in HPF led to increased ER stress levels, as reflected in upregulated ER stress markers BiP and ATF6α(N) (activated ATF6). Co-treatment with 4-PBA (2 mM), an ER stress inhibitor, reversed TGFβ1-induced increases in BiP and ATF6α(N) (Bip, ATF6α(P): n = 9 biologically independent samples per group, ATF6α(N): n = 12 biologically independent samples per group). b TXNDC5 mRNA was increased in response to TGFβ1 treatment, which was significantly attenuated by 4-PBA (n = 7,6,6 biologically independent samples). c Knockdown efficiency of lentiviral vectors carrying ATF6-targeted shRNA in HPF (n = 6 biologically independent samples per group). d TXNDC5 transcript was significantly increased in control (shScr), but not in ATF6-knockdown (shATF6), HPF following TGFβ1 treatment (n = 6 biologically independent samples per group). e Schematic illustration of the human TXNDC5 promoter luciferase reporter construct, which contains an ATF6-binding site. Deletion of the ATF6-binding site (TGACGTGG, + 642 to +653, ΔATF6) markedly reduced the transcriptional activity of the TXNDC5 promoter in response to TGFβ1 stimulation (WT TXNDC5: n = 16 in ctrl, 17 in TGFβ1 biologically independent samples, ΔATF6: n = 10 in ctrl, 11 in TGFβ1 biologically independent samples) (Data are presented as mean ± SEM, P value determined using two-tailed Mann–Whitney U test. Source data are provided as a Source Data file. n.s. non-significant, ctrl control, shATF6: ATF6 knockdown with shRNA).

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