Heat shock transcription factor 2 predicts mucosal healing and promotes mucosal repair of ulcerative colitis

Abstract

Background: Mucosal healing(MH) is a treatment goal in ulcerative colitis (UC). Our previous studies showed heat shock transcription factor 2 (HSF2) was positively correlated with the activity of UC and had anti-inflammatory potential in DSS-induced colitis, but the role of HSF2 in MH remains unknown. This study aimed to reveal the predictive value and mechanisms of HSF2 in the MH of UC.

Methods: Fecal samples were collected from 51 UC patients and 10 healthy controls. Correlation analyses among HSF2, fecal calprotectin(FC) and Mayo endoscopic subscore(MES) were conducted by Pearson correlation coefficient. Diagnostic accuracy and cutoffs to predict MH were analyzed by ROC curves. 231 UC patients were enrolled to verify the diagnostic validity of the cutoffs. HSF2 siRNA and HSF2-FLAG recombinant plasmids were transfected into HT-29 cells. IL-1β, TNF-α and TGF-β levels in supernatants were determined by ELISA. The expression and phosphorylation levels of MAPKs and Smad2/3 were detected by Western blotting.

Results: Positive correlations existed between HSF2 and MES (r = 0.81), FC and MES (r = 0.85), and HSF2 and FC (r = 0.91). Optimal cutoffs of HSF2 was 1.97 ng/ml (AUC 0.919) and that of FC was 678 µg/g (AUC 0.958). HSF2 and FC achieved high sensitivity (73.7% vs 84.2%) and negative predictive value (89.1% vs 93.9%). HSF2 decreased IL-1β and TNF-α secretion via suppression of MAPK signaling pathway activation. HSF2 promoted the expression of TGF-β via increasing phosphorylation of Smad2/3.

Conclusions: HSF2 may be a predictor of MH in UC patients. HSF2 inhibited inflammation and promoted mucosal repair.

Keywords:

• Ulcerative colitis
• mucosal healing
• heat shock transcription factor 2
• predictive value
• mechanisms

Disclosure statement

The authors declare that there is no conflict of interests in this study.

Author contributions

Y.L.W., J.K.N., and Y.L.M. conceived and designed the project. Y.L.W., J.W., M.J.L., and Y.T. recruited patients and collected specimens. J.K.N., F.R.Z., S.X.X., and W.W. conducted experiments. Y.S., K.H.W., and Y.L.M. analyzed and interpreted the data. Y.L.W. and J.K.N. drafted the manuscript. All authors read and approved the final manuscript.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (U1802282, 81660100, 81670501, 81960108), the Applied Basic Research Projects of Yunnan Province (2016FA033, 2019FE-001(036)), the Medicine Leading Talent of Health and Family Planning Commission of Yunnan Province (L-201607) and the Digestive Disease Prevention and Treatment Engineering Research Center of Yunnan Province.