PMID- 32538201 OWN - NLM STAT- MEDLINE DCOM- 20210629 LR - 20210629 IS - 1502-7708 (Electronic) IS - 0036-5521 (Linking) VI - 55 IP - 6 DP - 2020 Jun TI - Heat shock transcription factor 2 predicts mucosal healing and promotes mucosal repair of ulcerative colitis. PG - 677-686 LID - 10.1080/00365521.2020.1774924 [doi] AB - 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-1beta, TNF-alpha and TGF-beta 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 microg/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-1beta and TNF-alpha secretion via suppression of MAPK signaling pathway activation. HSF2 promoted the expression of TGF-beta via increasing phosphorylation of Smad2/3.Conclusions: HSF2 may be a predictor of MH in UC patients. HSF2 inhibited inflammation and promoted mucosal repair. FAU - Wen, Yunling AU - Wen Y AUID- ORCID: 0000-0002-8197-0599 AD - Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. FAU - Niu, Junkun AU - Niu J AD - Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. FAU - Zhang, Fengrui AU - Zhang F AD - Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. FAU - Wu, Jing AU - Wu J AD - Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. FAU - Li, Maojuan AU - Li M AD - Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. FAU - Sun, Yang AU - Sun Y AD - Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. FAU - Wang, Wen AU - Wang W AD - Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. FAU - Xia, Shuxian AU - Xia S AD - Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. FAU - Tan, Ying AU - Tan Y AD - Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. FAU - Wang, Kunhua AU - Wang K AD - Department of General Surgery, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. FAU - Miao, Yinglei AU - Miao Y AD - Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, China. LA - eng PT - Journal Article DEP - 20200613 PL - England TA - Scand J Gastroenterol JT - Scandinavian journal of gastroenterology JID - 0060105 RN - 0 (Biomarkers) RN - 0 (Heat-Shock Proteins) RN - 0 (Interleukin-1beta) RN - 0 (Leukocyte L1 Antigen Complex) RN - 0 (Transcription Factors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 142297-91-4 (HSF2 protein, human) SB - IM MH - Adult MH - Biomarkers/analysis/metabolism MH - Case-Control Studies MH - Colitis, Ulcerative/*metabolism/pathology MH - Colonoscopy MH - Feces/*chemistry MH - Female MH - HT29 Cells MH - Heat-Shock Proteins/genetics/*metabolism MH - Humans MH - Interleukin-1beta/metabolism MH - Intestinal Mucosa/*metabolism/pathology MH - Leukocyte L1 Antigen Complex/*analysis MH - Male MH - Middle Aged MH - ROC Curve MH - Severity of Illness Index MH - Transcription Factors/genetics/*metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Ulcerative colitis OT - heat shock transcription factor 2 OT - mechanisms OT - mucosal healing OT - predictive value EDAT- 2020/06/17 06:00 MHDA- 2021/06/30 06:00 CRDT- 2020/06/16 06:00 PHST- 2020/06/17 06:00 [pubmed] PHST- 2021/06/30 06:00 [medline] PHST- 2020/06/16 06:00 [entrez] AID - 10.1080/00365521.2020.1774924 [doi] PST - ppublish SO - Scand J Gastroenterol. 2020 Jun;55(6):677-686. doi: 10.1080/00365521.2020.1774924. Epub 2020 Jun 13.