Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder associated with progressive multi-organ complications affecting the pancreas, heart, white adipose tissue, and bone. Disease development and severity differ markedly between sexes and across stages of progression. A central pathological feature of T2DM is chronic hyperglycemia-induced oxidative stress, largely mediated by reactive oxygen species (ROS). Among ROS-producing enzymes, NADPH oxidase 4 (NOX4) is of particular interest due to its constitutive activity and close coupling to cellular metabolic fluxes.<\/p>\n
The overall aim of this project is to define the optimal temporal and tissue-specific window for targeted NOX4 inhibition during obesity-induced T2DM progression and to elucidate its organ- and sex-dependent effects. Using a combination of pharmacological NOX4 inhibition (setanaxib) and genetic NOX4 knockout models, the project systematically investigates early versus late intervention strategies across key metabolic organs. In parallel, it addresses a novel regulatory layer by exploring the interplay between NOX4 signaling and epitranscriptomic RNA modifications (m\u2076A\/m\u2076Am), which are emerging as critical modulators of gene expression, metabolic adaptation, and disease susceptibility.<\/p>\n
By integrating redox biology with epitranscriptomic regulation, this project aims to map dynamic, tissue- and sex-specific molecular changes during T2DM development, identify NOX4-dependent regulatory networks, and uncover potential circulating biomarkers of disease progression. The expected outcomes will advance mechanistic understanding of diabetic complications and support the development of precision, stage-specific therapeutic strategies targeting oxidative stress in T2DM.<\/p>\n
Supported by the Czech Science Foundation (project no. 26-20409S, 2026\u20132028; PI: Mark\u00e9ta Hlav\u00e1\u010dkov\u00e1, Ph.D.), in collaboration with the Laboratory of Pancreatic Islet Research and the Laboratory of Molecular Physiology of Bone, Institute of Physiology CAS.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":" Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder associated with progressive multi-organ complications affecting the pancreas, heart, white adipose tissue, and bone. Disease development and severity differ markedly between sexes and across stages of progression. A central pathological feature of T2DM is chronic hyperglycemia-induced oxidative stress, largely mediated by reactive oxygen species (ROS). […]<\/p>\n","protected":false},"author":8,"template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"oddeleni":[184],"poskytovatel":[],"stav-projektu":[209],"class_list":["post-53898","vyzkumny-projekt","type-vyzkumny-projekt","status-publish","hentry","oddeleni-developmental-cardiology","stav-projektu-current-projects"],"acf":[],"_links":{"self":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt\/53898","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt"}],"about":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/types\/vyzkumny-projekt"}],"author":[{"embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/users\/8"}],"version-history":[{"count":0,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt\/53898\/revisions"}],"wp:attachment":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/media?parent=53898"}],"wp:term":[{"taxonomy":"oddeleni","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/oddeleni?post=53898"},{"taxonomy":"poskytovatel","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/poskytovatel?post=53898"},{"taxonomy":"stav-projektu","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/stav-projektu?post=53898"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}