Compensatory renal hypertrophy following uninephrectomy is calcineurin-independent

Area of Science:

• Nephrology
• Molecular Biology
• Cellular Biology

Background:

• Calcineurin, a calcium-dependent phosphatase, regulates cellular processes including hypertrophy.
• Calcineurin inhibition or loss blocks pathological cardiac and diabetic renal hypertrophy.
• Calcineurin is not involved in exercise-induced physiological cardiac hypertrophy.

Purpose of the Study:

• To investigate calcineurin activation and its role in compensatory renal hypertrophy following uninephrectomy (UNX).
• To determine if calcineurin inhibition or knockout affects compensatory kidney growth.

Main Methods:

• Uninephrectomy (UNX) model in mice to induce compensatory renal hypertrophy.
• Measurement of calcineurin activity and nuclear factor of activated T cell (NFAT) transcriptional activity.
• Assessment of compensatory hypertrophy in wild-type (WT) mice, calcineurin-inhibited mice (cyclosporine), and calcineurin catalytic subunit knockout mice (CnAα-/- or CnAβ-/-).

Main Results:

• UNX induced ~15% kidney size increase without altering reactive oxygen species (ROS), Nox4, or transforming growth factor-β (TGF-β) expression.
• Total calcineurin activity and NFAT transcriptional activity were increased in the remaining kidney post-UNX.
• Cyclosporine treatment and calcineurin isoform knockout failed to inhibit compensatory renal hypertrophy.

Conclusions:

• Calcineurin is essential for pathological renal hypertrophy but not for compensatory renal hypertrophy following UNX.
• This finding differentiates signaling pathways involved in pathological versus compensatory renal growth.
• Understanding these distinct pathways may help identify targets for treating pathological conditions like diabetic nephropathy.