Immunohistochemical expression pattern of RIP5, FGFR1, FGFR2 and HIP2 in the normal human kidney development

Racetin, Anita; Raguž, Fila; Durdov, Merica Glavina; Kunac, Nenad; Saraga, Marijan; Sanna‐Cherchi, Simone; Šoljić, Violeta; Martinović, Vlatka; Petričević, Joško; Kostić, Sandra; Mardesic, Snjezana; Tomaš, Sandra Zekić; Kablar, Boris; Restović, Ivana; Lozić, Mirela; Filipović, Natalija; Saraga-Babić, Mirna; Vukojević, Katarina

doi:10.1016/j.acthis.2019.04.011

Cited by 15 publications

(18 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 FGFR1 has been known to be strongly expressed in the developing ureteric wall. 51 The FGFR finding in this study was variable. Statistical tests confirmed that significantly more FGFR-positive structures were seen in the megaureter group.…”

Section: Discussionmentioning

confidence: 58%

Evaluation of PGP 9.5, NGFR, TGFβ1, FGFR1, MMP-2, AT2R2, SHH, and TUNEL in Primary Obstructive Megaureter Tissue

Junga

Siņicins

Pētersons

et al. 2021

J Histochem Cytochem.

View full text Add to dashboard Cite

Primary obstructive megaureter (POM) morphogenesis is not fully known. The aim of the study was to evaluate the appearance of different factors that might take part in the pathogenesis of POM. Megaureter tissues of 14 children were stained with hematoxylin and eosin as well as with immunohistochemistry for protein gene product 9.5, nerve growth factor receptor, transforming growth factor beta 1 (TGFβ1), fibroblast growth factor receptor 1 (FGFR1), matrix metalloproteinase 2 (MMP-2), angiotensin 2 receptor type 2, and sonic hedgehog (SHH) protein. Apoptosis was detected by terminal dUTP nick-end labeling reaction. POM tissues revealed transitional epithelium with scattered vacuolization, submucosa with inflammatory cells, and focally vacuolized and chaotically organized muscle layers. Apoptosis, appearance of MMP-2, FGFR1, and SHH prevailed, but TGFβ1 positive cell number was lower in patients. Correlation between MMP-2 in epithelium and endothelium, FGFR1 and MMP-2 in epithelium, and TGFβ1 in epithelium and connective tissue in patients was detected. POM morphopathogenesis involves an apoptotic cell death of epithelium and smooth muscle as well as tissue degradation in epithelium and connective tissue of the ureter wall. The decrease of tissue growth through diminished TGFβ1 expression and stimulation of FGFR1 and MMP-2 suggests a disbalance of tissue remodelation in the megaureter wall:

show abstract

Section: Discussionmentioning

confidence: 58%

Evaluation of PGP 9.5, NGFR, TGFβ1, FGFR1, MMP-2, AT2R2, SHH, and TUNEL in Primary Obstructive Megaureter Tissue

Junga

Siņicins

Pētersons

et al. 2021

J Histochem Cytochem.

View full text Add to dashboard Cite

show abstract

“…Quantitative analyses were performed as we described previously [40,41]. ImageJ software (National Institutes of Health, Bethesda, MD, USA) was utilized for cell counting (only positive structures were used for counting, if any were present) and from the data, percentages of positive cells per structure were obtained.…”

Section: Quantification and Statistical Analysis Of Positive Cellsmentioning

confidence: 99%

CRKL, AIFM3, AIF, BCL2, and UBASH3A during Human Kidney Development

Lozić

Minarik

Racetin

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

We aimed to investigate the spatio-temporal expression of possible CAKUT candidate genes CRKL, AIFM3, and UBASH3A, as well as AIF and BCL2 during human kidney development. Human fetal kidney tissue was stained with antibodies and analyzed by fluorescence microscopy and RT-PCR. Quantification of positive cells was assessed by calculation of area percentage and counting cells in nephron structures. Results showed statistically significant differences in the temporal expression patterns of the examined markers, depending on the investigated developmental stage. Limited but strong expression of CRKL was seen in developing kidneys, with increasing expression up to the period where the majority of nephrons are formed. Results also lead us to conclude that AIFM3 and AIF are important for promoting cell survival, but only AIFM3 is considered a CAKUT candidate gene due to the lack of AIF in nephron developmental structures. Our findings imply great importance of AIFM3 in energy production in nephrogenesis and tubular maturation. UBASH3A raw scores showed greater immunoreactivity in developing structures than mature ones which would point to a meaningful role in nephrogenesis. The fact that mRNA and proteins of CRKL, UBASH3A, and AIFM3 were detected in all phases of kidney development implies their role as renal development control genes.

show abstract

“…Expressed in the cell membranes of maturing epithelia of the kidney, RIP5 colocalizes with FGFRs in the ureteric bud and metanephric mesenchyme, thus making it a significant determinant of human urinary tract development downstream of fibroblast growth factor (FGF) signaling [11][12][13]. RIP5 knockdown in human embryonic renal cells blocked FGFstimulated phosphorylation of extracellular signal-regulated kinase (Erk), the paramount signal downstream of receptor tyrosine kinases [11].…”

Section: Introductionmentioning

confidence: 99%

“…Our recent studies displayed that huntingtin-interacting protein 2 (HIP2), co-expressed with RIP5, is strongly expressed in glomeruli, the collecting system, and the urothelium of the developing human kidney [13].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Expression Pattern of FGFR1, FGFR2, RIP5, and HIP2 in Developing and Postnatal Kidneys of Dab1−/− (yotari) Mice

Kelam

Racetin

Katsuyama

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Immunohistochemical expression pattern of RIP5, FGFR1, FGFR2 and HIP2 in the normal human kidney development

Cited by 15 publications

References 43 publications

Evaluation of PGP 9.5, NGFR, TGFβ1, FGFR1, MMP-2, AT2R2, SHH, and TUNEL in Primary Obstructive Megaureter Tissue

Evaluation of PGP 9.5, NGFR, TGFβ1, FGFR1, MMP-2, AT2R2, SHH, and TUNEL in Primary Obstructive Megaureter Tissue

CRKL, AIFM3, AIF, BCL2, and UBASH3A during Human Kidney Development

Immunohistochemical Expression Pattern of FGFR1, FGFR2, RIP5, and HIP2 in Developing and Postnatal Kidneys of Dab1−/− (yotari) Mice

Contact Info

Product

Resources

About