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Zinc deficiency is closely associated with CKD, evidenced by its link to renal fibrosis.\u00a0Recently, local lactic acidosis has been\u00a0demonstrated to\u00a0promote renal fibrosis. Under zinc-deficient conditions,\u00a0mitochondrial function\u00a0is\u00a0compromised and abnormal lactate metabolism might be induced\u00a0potentially. However, it remains unclear whether zinc deficiency leads to renal fibrosis\u00a0through local lactic acidosis. Zinc deficiency rat models were successfully established by feeding zinc-deficient diet. Western blot, qPCR, IHC, and other experiments were employed to investigate the key markers and molecular mechanisms of glomerulosclerosis and renal interstitial fibrosis. Our results\u00a0indicate that zinc deficiency reduces specific markers of podocytes (podocalyxin, WT1, and nephrin) and\u00a0activates the Wnt3a\/\u03b2-catenin pathway, a key pathway in podocyte injury. Concurrently, glomerulosclerosis is indicated by increased urinary microalbumin and serum creatinine levels along with histological alteration observed through PAS and Masson staining in zinc-deficient rats. Furthermore, various degrees of upregulation for several markers of interstitial fibrosis including \u03b1-SMA, FN1 and collagen III are also revealed. These findings were further confirmed by Masson staining and IHC. Additionally, alterations in four markers in the EMT process, N-cadherin, E-cadherin, Vimentin, and snail, were consistent with expectations. We then confirmed the activation of the non-canonical TGF-\u03b21 pathway known as the PI3K\/AKT\/mTOR pathway. An elevation in renal ROS levels accompanied by increased mitochondrial marker cytochrome C expression as well as an elevated NADH\/NAD\u2009+\u2009ratio is also observed within the kidneys. Furthermore, the activity of both MMP\/TIMP system and fibrinolytic system was abnormally enhanced under zinc deficiency conditions. Finally, we find zinc supplementation could significantly ameliorate relevant pathological alterations induced by zinc deficiency. These results collectively point that zinc deficiency causes podocyte damage ultimately resulting in glomerulosclerosis via accumulation of ROS and induces interstitial fibrosis via lactic acidosis.<\/jats:p>","DOI":"10.1007\/s12011-024-04306-1","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:01:26Z","timestamp":1721347286000},"page":"2084-2098","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["RETRACTED ARTICLE: Zinc Deficiency Causes Glomerulosclerosis and Renal Interstitial Fibrosis Through Oxidative Stress and Increased Lactate Metabolism in Rats"],"prefix":"10.1007","volume":"203","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2075-4371","authenticated-orcid":false,"given":"Zixuan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningxu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"4306_CR1","doi-asserted-by":"publisher","first-page":"1500s","DOI":"10.1093\/jn\/130.5.1500S","volume":"130","author":"RS MacDonald","year":"2000","unstructured":"MacDonald RS (2000) The role of zinc in growth and cell proliferation. 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