{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T21:56:53Z","timestamp":1778795813129,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Diabetic nephropathy (DN) is a leading cause of end-stage renal disease and continues to be a threat to patients with diabetes. Dysfunction of glomerular mesangial cells (GMCs) is the main contributing factor to glomerulosclerosis, which is a pathological feature of DN. The epigenetic factor ASH2L has long been thought to be a transcriptional activator, but its function and involvement in diabetic nephropathy is still unclear. Here, we investigated the effect of ASH2L on the regulation of fibrosis and inflammation induced by high glucose in mouse mesangial cells (mMCs). We observed that ASH2L expression is increased in high glucose-induced mMCs, while loss of ASH2L alleviated fibrosis and inflammation. Furthermore, ASH2L-mediates H3K4me3 of the homeodomain-interacting protein kinase 2 (HIPK2) promoter region, which is a contributor to fibrosis in the kidneys and promotes its transcriptional expression. Similar to loss of ASH2L, silencing HIPK2 also inhibited fibrosis and inflammation. In addition, ASH2L and HIPK2 are upregulated in the kidneys of both streptozocin-induced and db\/db mouse. In conclusion, we uncovered the crucial role of ASH2L in high glucose-induced fibrosis and inflammation, suggesting that ASH2L regulation may be an attractive approach to attenuate the progression of DN.<\/jats:p>","DOI":"10.3390\/genes13122244","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T04:05:24Z","timestamp":1669781124000},"page":"2244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["ASH2L Aggravates Fibrosis and Inflammation through HIPK2 in High Glucose-Induced Glomerular Mesangial Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Wen","family":"Zhong","sequence":"first","affiliation":[{"name":"School of pharmacy, Fudan University, Shanghai 201203, China"},{"name":"Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Hong","sequence":"additional","affiliation":[{"name":"Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yejun","family":"Dong","sequence":"additional","affiliation":[{"name":"Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhui","family":"Li","sequence":"additional","affiliation":[{"name":"Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenxi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9972-8215","authenticated-orcid":false,"given":"Xinhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nrneph.2017.31","article-title":"The role of the complement system in diabetic nephropathy","volume":"13","author":"Flyvbjerg","year":"2017","journal-title":"Nat. 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