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Intravascular Delivery of Biologics to the Rat Kidney
Published on: September 1, 2016
Localization of discoidin domain receptors in rat kidney
Rutha Lee1, Keith E Eidman, Stefan M Kren
1Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, Minn., USA.
Background/Aim:
The discoidin domain receptors (DDRs) DDR1 and DDR2 are cardinal members of a receptor tyrosine kinase subfamily, activated by collagens. They are candidate effectors in tissue injury and fibrosis. We investigated the DDR expression in normal and remnant rat kidneys.
Methods:
The DDR expression in kidney and other tissues was examined by indirect immunofluorescence, immunoblotting, and ribonuclease protection assays. The expression patterns in remnant and control kidneys were compared at 2-, 4-, and 8-week time points, following induction of injury.
Results:
DDR1 is expressed in basolateral membranes of select nephron segments, from the connecting tubule to the renal papilla. DDR2 is expressed in apical membranes of select nephron segments, from the loop of Henle to the macula densa. The DDR1 protein expression is upregulated within the glomeruli of remnant kidneys. The distribution of DDR2 in remnant kidneys is similar to that in controls. The DDR mRNA levels in remnant and control kidneys were not significantly different, at any time point.
Conclusions:
The DDR1 localization in the rat kidney is consistent with roles in cell-matrix interactions. Upregulation within glomeruli of remnant kidneys suggests the possibility of additional roles in kidney injury. The DDR2 localization in adult rat kidneys is inconsistent with roles in cell-matrix interactions.
Insights
Discoidin domain receptors (DDRs) DDR1 and DDR2 are receptor tyrosine kinases. DDR1 upregulation in injured rat kidneys suggests a role in kidney injury, while DDR2
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Discoidin domain receptors (DDRs), DDR1 and DDR2, are receptor tyrosine kinases activated by collagens.
- DDRs are implicated in tissue injury and fibrosis.
- Investigated DDR expression in normal and injured rat kidneys.
Purpose of the Study:
- To investigate discoidin domain receptor (DDR) expression in normal and remnant rat kidneys.
- To determine the localization and regulation of DDR1 and DDR2 in kidney injury models.
Main Methods:
- Examined DDR expression using indirect immunofluorescence, immunoblotting, and ribonuclease protection assays.
- Compared DDR expression patterns in remnant and control rat kidneys at 2, 4, and 8 weeks post-injury.
Main Results:
- DDR1 localized to basolateral membranes of specific nephron segments; DDR2 localized to apical membranes of other segments.
- DDR1 protein expression was upregulated in glomeruli of remnant kidneys.
- DDR mRNA levels did not significantly differ between remnant and control kidneys.
Conclusions:
- DDR1 localization supports its role in kidney cell-matrix interactions and suggests involvement in kidney injury.
- DDR2 localization in adult rat kidneys is not consistent with cell-matrix interaction roles.
- Further research is warranted to elucidate the specific functions of DDR1 and DDR2 in renal pathophysiology.
