PMID- 38132291 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231224 IS - 2079-7737 (Print) IS - 2079-7737 (Electronic) IS - 2079-7737 (Linking) VI - 12 IP - 12 DP - 2023 Nov 24 TI - Sja-Let-7 Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in a Mouse Model via Col1alpha2. LID - 10.3390/biology12121465 [doi] LID - 1465 AB - Liver fibrosis (LF) is a chronic progressive disease with no definitive treatment. The aim of this study was to assess helminth-derived molecules as potential therapeutic targets to prevent or reverse LF. A mouse model of carbon tetrachloride (CCL(4))-induced LF was established and sja-let-7 was overexpressed by treatment with a miRNA agomir once per week. After four weeks, serum biochemistry, hepatic hydroxyproline content measurements, liver histology, mRNA expression profiling of fibrotic markers, the dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH) were performed. Administration of the sja-let-7 agomir markedly ameliorated hepatosplenomegaly and reduced the liver hydroxyproline content. Liver histological analysis showed significant reductions in collagen deposition in the sja-let-7 agomir-treated mice. Additionally, the mRNA levels of both pro-fibrotic markers and pro-inflammatory cytokines were diminished after treatment. Furthermore, the dual-luciferase reporter assay and FISH identified the alpha2 chain of collagen type 1 (Col1alpha2) as the direct target of sja-let-7. Accordingly, the progression of LF was attenuated by targeting Col1alpha2 and the TGF-beta/Smad signaling pathway. FAU - Zhong, Haoran AU - Zhong H AUID- ORCID: 0000-0003-0967-9542 AD - National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. AD - Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. FAU - Dong, Bowen AU - Dong B AD - National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. AD - Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. FAU - Zhu, Danlin AU - Zhu D AD - National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. AD - Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. FAU - Li, Hao AU - Li H AD - National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. AD - Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. FAU - Lu, Ke AU - Lu K AD - National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. AD - Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. FAU - Fu, Zhiqiang AU - Fu Z AD - National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. AD - Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. FAU - Liu, Jinming AU - Liu J AD - National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. AD - Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. FAU - Jin, Yamei AU - Jin Y AD - National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. AD - Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. LA - eng GR - 20ZR1469300/Natural Science Foundation of Shanghai/ GR - 31672245/Chinese National Natural Science Foundation/ PT - Journal Article DEP - 20231124 PL - Switzerland TA - Biology (Basel) JT - Biology JID - 101587988 PMC - PMC10740823 OTO - NOTNLM OT - Col1alpha2 OT - TGF-beta/Smad signaling pathway OT - hepatic stellate cell OT - liver fibrosis OT - sja-let-7 COIS- The authors declare no conflict of interest. EDAT- 2023/12/22 12:42 MHDA- 2023/12/22 12:43 PMCR- 2023/11/24 CRDT- 2023/12/22 09:04 PHST- 2023/10/17 00:00 [received] PHST- 2023/11/07 00:00 [revised] PHST- 2023/11/17 00:00 [accepted] PHST- 2023/12/22 12:43 [medline] PHST- 2023/12/22 12:42 [pubmed] PHST- 2023/12/22 09:04 [entrez] PHST- 2023/11/24 00:00 [pmc-release] AID - biology12121465 [pii] AID - biology-12-01465 [pii] AID - 10.3390/biology12121465 [doi] PST - epublish SO - Biology (Basel). 2023 Nov 24;12(12):1465. doi: 10.3390/biology12121465.