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

Int J Mol Sci. 2021 Aug 25;22(17):9183. doi: 10.3390/ijms22179183.

Abstract

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.

Keywords: AIF; AIFM3; BCL2; CRKL; UBASH3A; development; kidney.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Apoptosis Inducing Factor / genetics
  • Apoptosis Inducing Factor / metabolism
  • Fetus / embryology
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Infant
  • Infant, Newborn
  • Kidney / embryology
  • Kidney / growth & development
  • Kidney / metabolism*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Urogenital Abnormalities / genetics*
  • Vesico-Ureteral Reflux / genetics*

Substances

  • AIFM1 protein, human
  • AIFM3 protein, human
  • Adaptor Proteins, Signal Transducing
  • Apoptosis Inducing Factor
  • BCL2 protein, human
  • CRKL protein
  • Mitochondrial Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • UBASH3A protein, human

Supplementary concepts

  • Cakut