| Title: |
Liver secretin receptor predicts portoenterostomy outcomes and liver injury in biliary atresia |
| Authors: |
Godbole, Nimish; Nyholm, Iiris; Hukkinen, Maria; Davidson, Joseph R.; Tyraskis, Athanasios; Lohi, Jouko; Heikkilä, Päivi; Eloranta, Katja; Pihlajoki, Marjut; Davenport, Mark; Heikinheimo, Markku; Kyrönlahti, Antti; Pakarinen, Mikko P. |
| Contributors: |
Children's Hospital; University of Helsinki; HUS Children and Adolescents; Lastenkirurgian yksikkö; HUSLAB; Department of Pathology; Medicum; Helsinki One Health (HOH); Clinicum; Developmental and tumor biology research group; Faculty Common Matters (Faculty of Medicine); HUS Radiology and Pathology |
| Publisher Information: |
Nature Research |
| Publication Year: |
2022 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
GENE-EXPRESSION; FIBROSIS; PROLIFERATION; PATHOGENESIS; INDEX; General medicine; internal medicine and other clinical medicine |
| Description: |
Biliary atresia (BA) is a chronic neonatal cholangiopathy characterized by fibroinflammatory bile duct damage. Reliable biomarkers for predicting native liver survival (NLS) following portoenterostomy (PE) surgery are lacking. Herein we explore the utility of 22 preidentified profibrotic molecules closely connected to ductular reaction (DR) and prevailing after successful PE (SPE), in predicting PE outcomes and liver injury. We used qPCR and immunohistochemistry in a BA cohort including liver samples obtained at PE (n = 53) and during postoperative follow-up after SPE (n = 25). Of the 13 genes over-expressed in relation to cholestatic age-matched controls at PE, only secretin receptor (SCTR) expression predicted cumulative 5-year NLS and clearance of jaundice. Patients in the highest SCTR expression tertile showed 34-55% lower NLS than other groups at 1-5 years after PE (P = 0.006-0.04 for each year). SCTR expression was also significantly lower [42 (24-63) vs 75 (39-107) fold, P = 0.015] among those who normalized their serum bilirubin after PE. Liver SCTR expression localized in cholangiocytes and correlated positively with liver fibrosis, DR, and transcriptional markers of fibrosis (ACTA2) and cholangiocytes (KRT7, KRT19) both at PE and after SPE. SCTR is a promising prognostic marker for PE outcomes and associates with liver injury in BA. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Sigrid Juselius Foundation (MPP, MH), Finnish Pediatric Research Foundation (MPP), Helsinki University Hospital Fund (MPP, MH), Finska Lakaresallskapet (MH). The funding sources were not involved in conduct of the research, study design, collection, analysis or interpretation of the data, in preparation of article or decision to submit the article for publication.; https://hdl.handle.net/10138/344351; 000790941900095 |
| Availability: |
https://hdl.handle.net/10138/344351 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.9EA8941E |
| Database: |
BASE |