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We suggested that the liver first responded to chronic injuries with gradual changes, then reached the critical state and ultimately resulted in cirrhosis rapidly. This study aimed to identify the tipping point and key molecules driving liver fibrosis progression. Mice model of liver fibrosis was induced by thioacetamide (TAA), and liver tissues were collected at different time\u2010points post\u2010TAA administration. By dynamic network biomarker (DNB) analysis on the time series of liver transcriptomes, the week 9 post\u2010TAA treatment (pathologically relevant to bridging fibrosis) was identified as the tipping point just before the significant fibrosis transition, with 153 DNB genes as key driving factors. The DNB genes were functionally enriched in fibrosis\u2010associated pathways, in particular, in the top\u2010ranked DNB genes, Tgfb3 negatively regulated Mmp13 in the interaction path and they formed a bistable switching system from a dynamical perspective. In the <jats:italic>in vitro<\/jats:italic> study, Tgfb3 promoted fibrogenic genes and down\u2010regulate Mmp13 gene transcription in an immortalized mouse HSC line JS1 and a human HSC line LX\u20102. The presence of a tipping point during liver fibrogenesis driven by DNB genes marks not only the initiation of significant fibrogenesis but also the repression of the scar resolution.<\/jats:p>","DOI":"10.1111\/jcmm.16140","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T05:08:40Z","timestamp":1606972120000},"page":"867-879","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Tgfb3 and Mmp13 regulated the initiation of liver fibrosis progression as dynamic network biomarkers"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-8725","authenticated-orcid":false,"given":"Jinsheng","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhong Shan Hospital Fu Dan University Shanghai Institute of Liver Diseases  Shanghai 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