PMID- 35216141 OWN - NLM STAT- MEDLINE DCOM- 20220315 LR - 20220315 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 4 DP - 2022 Feb 11 TI - Immunohistochemical Expression Pattern of FGFR1, FGFR2, RIP5, and HIP2 in Developing and Postnatal Kidneys of Dab1(-/-) (yotari) Mice. LID - 10.3390/ijms23042025 [doi] LID - 2025 AB - This study aimed to explore how Dab1 gene functional silencing influences the spatial and temporal expression patterns of fibroblast growth factor receptor 1 (FGFR1), fibroblast growth factor receptor 2 (FGFR2), receptor-interacting protein kinase 5 (RIP5), and huntingtin-interacting protein 2 (HIP2) in the developing and postnatal kidneys of the yotari mice as potential determinants of normal kidney formation and function. Dab1(-/-) animal kidneys exhibit diminished FGFR1/FGFR2 expression in all examined developmental stages, whereas RIP5 cell immunoreactivity demonstrated negligible variation. The HIP2 expression revealed a discernible difference during the postnatal period, where we noted a significant decrease in almost all the observed kidney structures of yotari animals. An extracellular signal-regulated kinase (Erk1/2) and mammalian target of rapamycin (mTOR) expression in yotari kidneys decreased in embryonic and postnatal developmental phases for which we can hypothesize that the Erk1/2 signaling pathway in the yotari mice kidneys is dependent on Reelin with Dab1 only partially implicated in Reelin-mediated MEK/Erk1/2 activation. The impairment of FGFR1 and FGFR2 expression suggests the involvement of the observed markers in generating the CAKUT phenotype resulting in renal hypoplasia. Our study demonstrates the critical role of HIP2 in reducing cell death throughout nephrogenesis and maturation in wild-type mice and indicates a possible connection between decreased HIP2 expression in postnatal kidney structures and observed podocyte injury in yotari. Our results emphasize the crucial function of the examined markers throughout normal kidney development and their potential participation in kidney pathology and diagnostics, where they might serve as biomarkers and therapeutic targets. FAU - Kelam, Nela AU - Kelam N AUID- ORCID: 0000-0002-6529-5474 AD - Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia. FAU - Racetin, Anita AU - Racetin A AD - Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia. AD - Department of Medical Genetics, University of Mostar School of Medicine, 88000 Mostar, Bosnia and Herzegovina. FAU - Katsuyama, Yu AU - Katsuyama Y AD - Department of Anatomy, Shiga University of Medical Science, Otsu 520-2192, Japan. FAU - Vukojevic, Katarina AU - Vukojevic K AUID- ORCID: 0000-0003-2182-2890 AD - Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia. AD - Department of Medical Genetics, University of Mostar School of Medicine, 88000 Mostar, Bosnia and Herzegovina. FAU - Kostic, Sandra AU - Kostic S AD - Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia. LA - eng GR - IP-06-2016-2575/Croatian Science Foundation/ PT - Journal Article DEP - 20220211 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers) RN - 0 (Dab1 protein, mouse) RN - 0 (Nerve Tissue Proteins) RN - EC 2.3.2.23 (Ube2k protein, mouse) RN - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes) RN - EC 2.7.10.1 (Fgfr1 protein, mouse) RN - EC 2.7.10.1 (Fgfr2 protein, mouse) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2) RN - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases) RN - Cakut SB - IM MH - Animals MH - Biomarkers/metabolism MH - Kidney/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Nerve Tissue Proteins/*metabolism MH - Phenotype MH - Receptor, Fibroblast Growth Factor, Type 1/*metabolism MH - Receptor, Fibroblast Growth Factor, Type 2/*metabolism MH - Receptor-Interacting Protein Serine-Threonine Kinases/*metabolism MH - Signal Transduction/physiology MH - Ubiquitin-Conjugating Enzymes/*metabolism MH - Urogenital Abnormalities/metabolism MH - Vesico-Ureteral Reflux/metabolism PMC - PMC8879463 OTO - NOTNLM OT - Erk1/2 OT - FGFR1 OT - FGFR2 OT - HIP2 OT - RIP5 OT - kidney development OT - mTOR OT - yotari mice COIS- The authors declare no conflict of interest. EDAT- 2022/02/27 06:00 MHDA- 2022/03/16 06:00 PMCR- 2022/02/11 CRDT- 2022/02/26 01:07 PHST- 2021/12/23 00:00 [received] PHST- 2022/02/04 00:00 [revised] PHST- 2022/02/10 00:00 [accepted] PHST- 2022/02/26 01:07 [entrez] PHST- 2022/02/27 06:00 [pubmed] PHST- 2022/03/16 06:00 [medline] PHST- 2022/02/11 00:00 [pmc-release] AID - ijms23042025 [pii] AID - ijms-23-02025 [pii] AID - 10.3390/ijms23042025 [doi] PST - epublish SO - Int J Mol Sci. 2022 Feb 11;23(4):2025. doi: 10.3390/ijms23042025.