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Our previous study demonstrated that insulin-like growth factor-binding protein 5 (IGFBP-5) promotes glycolytic reprogramming in vascular endothelial cells (ECs) and exacerbates renal inflammation in diabetic kidney disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human renal proximal tubular epithelial cells (HK-2) and human umbilical vein endothelial cells (HUVECs) were used. A co-culture system was employed to investigate endothelial cell\u2013tubular epithelial cell (EC-TEC) crosstalk. Unilateral ureteral obstruction (UUO) and aristolochic acid nephropathy (ANN) models were established in wild-type (WT), global IGFBP-5\u2212\/\u2212 and endothelial-specific Tie-2 Cre;IGFBP-5\u2212\/\u2212 mice. Expression levels of IGFBP-5, TGF-\u03b21 and fibrosis markers were assessed to investigate the role of IGFBP-5 in renal fibrogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum IGFBP-5 levels were significantly elevated in patients with CKD. Genetic ablation of IGFBP-5 attenuated renal fibrosis in murine models, demonstrating its critical role in fibrogenesis. IGFBP-5 was predominantly expressed in ECs and endothelial-specific deletion delayed renal fibrosis progression via suppression of the TGF-\u03b21\/Smad3 pathway. In vitro, endothelial-derived IGFBP-5 promoted a profibrotic phenotypic transformation in TECs through AKT-mediated phosphorylation of the TGF-\u03b21\/Smad3 axis. Conversely, TGF-\u03b21 stimulated IGFBP-5 biosynthesis and secretion in ECs via the ERK signalling pathway, establishing a self-amplifying feedback loop. This reciprocal IGFBP-5\/TGF-\u03b21 crosstalk between ECs and TECs was confirmed in co-culture experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings reveal a novel EC\u2013TEC crosstalk axis mediated by reciprocal IGFBP-5\/TGF-\u03b21 signalling, which is a critical driver of renal fibrosis. IGFBP-5 emerges as a promising therapeutic target for inhibiting renal fibrogenesis in CKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfaf179","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T11:59:43Z","timestamp":1756555183000},"page":"531-544","source":"Crossref","is-referenced-by-count":5,"title":["IGFBP-5\/TGF-\u03b21 mediated crosstalk between endothelial and tubular epithelial cells promotes interstitial fibrosis"],"prefix":"10.1093","volume":"41","author":[{"given":"Shuqiang","family":"Wang","sequence":"first","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research Department of Nephrology, , Beijing ,","place":["China"]},{"name":"Peking University Shenzhen Hospital Department of Nephrology, , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Song","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research Department of Nephrology, , Beijing ,","place":["China"]},{"name":"Capital Medical University Electric Teaching Hospital Department of Nephrology, , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Chi","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research Department of Nephrology, , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangning","family":"Fu","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research Department of Nephrology, , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Capital Medical University Electric Teaching Hospital Department of Nephrology, , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Geng","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research Department of Nephrology, , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research Department of Nephrology, , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Cai","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research Department of Nephrology, , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8774-6021","authenticated-orcid":false,"given":"Xiangmei","family":"Chen","sequence":"additional","affiliation":[{"name":"First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research Department of Nephrology, , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Cijiang","family":"He","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai Division of Nephrology, Department of Medicine, , New York, NY ,","place":["USA"]},{"name":"Renal Section, James J. 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