{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T13:59:30Z","timestamp":1784210370816,"version":"3.55.0"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,9,10]],"date-time":"2014-09-10T00:00:00Z","timestamp":1410307200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the topic of this review?<\/jats:bold><\/jats:p>\n<jats:p>Through reference to specific lines of investigation, this review sets out the case for how understanding the drivers and endogenous counter\u2010regulators of inflammatory and fibrotic responses can identify novel targets for inhibition or mimicry in diabetic kidney disease.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What advances does it highlight?<\/jats:bold><\/jats:p>\n<jats:p>The review highlights the potential of induced in high glucose\u20101 (IHG\u20101) and induced in high glucose\u20102 (IHG\u20102\/Grem1) to act as drugable targets in transforming growth factor\u2010<jats:italic>\u03b2<\/jats:italic> superfamily signalling in diabetic kidney disease. It also describes the preclinical evidence base for the fibrosupressant effects of the resolvent lipoxin series of eicosanoids in diabetic kidney disease, highlighting the role of a novel and specific microRNA\u2010based effect on transforming growth factor\u2010<jats:italic>\u03b2<\/jats:italic>1 signalling.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Diabetic kidney disease occurs in &gt;30% of patients with type\u00a02 diabetes mellitus and is characterized at source by a maladaptive response in the renal parenchyma to exposure to a glucotoxic\u2013lipotoxic diabetic milieu that courses coincident with hypertension. The consequence of these maladaptive responses is progressive renal injury, which is exacerbated by the development of a chronic inflammatory infiltrate associated with the development of tubulointerstitial fibrosis. The evolution of tubulointerstitial fibrosis is correlated with the loss of functional renal mass and descent towards renal failure. Transforming growth factor\u2010<jats:italic>\u03b2<\/jats:italic>1 (TGF\u2010<jats:italic>\u03b2<\/jats:italic>1) is a recognized mediator of the profibrotic response of mesangial cells and renal tubular epithelial cells to hyperglycaemia. While euglycaemia remains the goal in the treatment of type\u00a02 diabetes mellitus, the prevention, arrest and reversal of microvascular complications, such as diabetic kidney disease, may be assisted by pharmacological modulation of the effectors of glucotoxicity, such as TGF\u2010<jats:italic>\u03b2<\/jats:italic>1. This review focuses on describing how, through reductionist <jats:italic>in vitro<\/jats:italic> experimentation focusing on TGF\u2010<jats:italic>\u03b2<\/jats:italic>1\u2010related responses to hyperglycaemia, we have identified induced in high glucose\u20101 (IHG\u20101), induced in high glucose\u20102 (IHG\u20102\/Grem1) and the lipoxin\u2010inducible microRNA let\u20107c as potential targets for harnessing new therapeutic approaches to limit the bioactivity of TGF\u2010<jats:italic>\u03b2<\/jats:italic>1 in diabetic kidney disease.<\/jats:p><\/jats:sec>","DOI":"10.1113\/expphysiol.2014.078774","type":"journal-article","created":{"date-parts":[[2014,8,2]],"date-time":"2014-08-02T06:56:03Z","timestamp":1406962563000},"page":"1154-1162","source":"Crossref","is-referenced-by-count":9,"title":["Targeting cellular drivers and counter\u2010regulators of hyperglycaemia\u2010 and transforming growth factor\u2010<i>\u03b2<\/i>1\u2010associated profibrotic responses in diabetic kidney disease"],"prefix":"10.1113","volume":"99","author":[{"given":"Neil G.","family":"Docherty","sequence":"first","affiliation":[{"name":"Diabetes Complications Research Centre Conway Institute of Biomolecular and Biomedical Research School of Medicine and Medical Sciences University College Dublin  Belfield Dublin 4 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Murphy","sequence":"additional","affiliation":[{"name":"Diabetes Complications Research Centre Conway Institute of Biomolecular and Biomedical Research School of Medicine and Medical Sciences University College Dublin  Belfield Dublin 4 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finian","family":"Martin","sequence":"additional","affiliation":[{"name":"Diabetes Complications Research Centre Conway Institute of Biomolecular and Biomedical Research School of Medicine and Medical Sciences University College Dublin  Belfield Dublin 4 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