{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:10:24Z","timestamp":1787987424723,"version":"build-2784847793"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Mitogen-activated protein kinases (p38, JNK, ERK1\/2) regulate key cellular processes essential for kidney development. Disruptions in these signaling pathways can lead to congenital anomalies of the kidney and urinary tract (CAKUT), a major cause of pediatric kidney disease. This study investigates and compares the expression of these molecules in normal fetal kidneys and CAKUT-affected tissues. Materials and Methods: Forty-three human fetal kidney samples, including controls and specimens with horseshoe, hypoplastic, and dysplastic kidneys, were analyzed across developmental phases 2\u20134 using immunofluorescence. Quantitative image analysis and statistical comparisons were performed between developmental stages and phenotypes. Results: ERK1\/2 expression increased during late development in control kidneys but was significantly reduced in hypoplastic kidneys. p38 showed phase-dependent alterations, with early upregulation in dysplastic kidneys and late elevation in horseshoe kidneys. JNK exhibited significant phase-dependent upregulation in horseshoe kidneys. P38 displayed dynamic expression associated with nephron maturation. Conclusions: MAPK pathways show distinct developmental and phenotype-specific expression patterns in human fetal kidneys. These differences reflect divergent pathogenic mechanisms in CAKUT and may support improved molecular characterization of congenital renal anomalies.<\/jats:p>","DOI":"10.3390\/medicina62030549","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:13:14Z","timestamp":1773659594000},"page":"549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Expression of ERK1\/2, p38, and JNK in Normal Kidney Development and CAKUT"],"prefix":"10.3390","volume":"62","author":[{"given":"Ivona","family":"Letica","sequence":"first","affiliation":[{"name":"Department of Pediatric Nephrology, University Clinical Hospital Mostar, 88000 Mostar, Bosnia and Herzegovina"},{"name":"School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6953-0135","authenticated-orcid":false,"given":"Petar","family":"Todorovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricija","family":"Bajt","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3452-389X","authenticated-orcid":false,"given":"Nikola","family":"Pavlovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6529-5474","authenticated-orcid":false,"given":"Nela","family":"Kelam","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1158-7965","authenticated-orcid":false,"given":"Marjana Jerkovi\u0107","family":"Ragu\u017e","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina"},{"name":"Department of Neonatology, University Clinical Hospital Mostar, 88000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-8237","authenticated-orcid":false,"given":"Ivanka","family":"Mikuli\u0107","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnostics, University Clinical Hospital Mostar, 88000 Mostar, Bosnia and Herzegovina"},{"name":"Faculty of Pharmacy, 88000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludvig","family":"Letica","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Clinical Hospital Mostar, 88000 Mostar, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6389-5604","authenticated-orcid":false,"given":"Sandra","family":"Kosti\u0107","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2182-2890","authenticated-orcid":false,"given":"Katarina","family":"Vukojevi\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina"},{"name":"Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia"},{"name":"Center for Translational Research in Biomedicine, School of Medicine, University of Split, 21000 Split, Croatia"},{"name":"Mediterranean Institute for Life Sciences, University of Split, Me\u0161trovi\u0107evo \u0160etali\u0161te 45, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Racetin","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.siny.2017.01.001","article-title":"Renal development in the fetus and premature infant","volume":"22","author":"Rosenblum","year":"2017","journal-title":"Semin. 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