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As a cardinal event of diabetic kidney disease (DKD<\/jats:styled-content>), whether the podocyte abnormalities are associated with IL<\/jats:styled-content>\u20106 signalling, especially classic or trans\u2010signalling respectively, remains unclear. In this study, we identified that the circulatory IL<\/jats:styled-content>\u20106, soluble IL<\/jats:styled-content>\u20106R (sIL<\/jats:styled-content>\u20106R) and soluble glycoprotein 130 (sgp130) levels are elevated in patients with DKD<\/jats:styled-content>. The expressions of membrane\u2010bound IL<\/jats:styled-content>\u20106R (mIL<\/jats:styled-content>\u20106R), sIL<\/jats:styled-content>\u20106R and gp130 are enhanced in kidney cortex of diabetic mice accompanying with activated STAT<\/jats:styled-content>3 by tyrosine 705 residue phosphorylation, while not serine 727. Above data infer both classic signalling and trans\u2010signalling of IL<\/jats:styled-content>\u20106 are activated during DKD<\/jats:styled-content>. In cultured podocyte, high glucose (HG<\/jats:styled-content>) up\u2010regulates the expression of mIL<\/jats:styled-content>\u20106R and gp130, as well as STAT<\/jats:styled-content>3 tyrosine 705 phosphorylation, in a time\u2010dependent manner. Entirely blocking IL<\/jats:styled-content>\u20106 signalling by gp130 shRNA<\/jats:styled-content>, gp130 or IL<\/jats:styled-content>\u20106 neutralizing antibodies attenuates HG<\/jats:styled-content>\u2010induced podocyte injury. Interestingly, either inhibiting IL<\/jats:styled-content>\u20106 classic signalling by mIL<\/jats:styled-content>\u20106R shRNA<\/jats:styled-content> or suppressing its trans\u2010signalling using sgp130 protein dramatically alleviates HG<\/jats:styled-content>\u2010induced podocyte injury, suggesting both IL<\/jats:styled-content>\u20106 classic signalling and trans\u2010signalling play a detrimental role in HG<\/jats:styled-content>\u2010induced podocyte injury. Additionally, activation of IL<\/jats:styled-content>\u20106 classic or trans\u2010signalling aggravates podocyte damage in vitro. In summary, our observations demonstrate that the activation of either IL<\/jats:styled-content>\u20106 classic or trans\u2010signalling advances podocyte harming under hyperglycaemia. Thus, suppressing IL<\/jats:styled-content>\u20106 classic and trans\u2010signalling simultaneously may be more beneficial in podocyte protection and presents a novel therapeutic target for DKD.<\/jats:p>","DOI":"10.1111\/jcmm.13314","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T18:55:28Z","timestamp":1504810528000},"page":"251-260","source":"Crossref","is-referenced-by-count":30,"title":["The classic signalling and trans\u2010signalling of interleukin\u20106 are both injurious in podocyte under high glucose exposure"],"prefix":"10.1111","volume":"22","author":[{"given":"Chun\u2010Tao","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Nephrology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Nephrology Union Hospital Tongji Medical 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