Question: 

Loss of kidney tissue results in a hypertrophy of the remaining intact nephrons. The mechanisms inducing this compensatory renal hypertrophy are not clearly defined. Since loss of kidney tissue results in glomerular hyperfiltration and in increases in tubular load and tubular flow velocity in proximal tubules, we tested whether tubular flow induces hypertrophy of proximal tubular cells (PTC).

Methods: 

LLCPK₁ and primary proximal tubular cells of mice were superfused at different flow velocities (up to 2 mm/s) to mimic the elevated tubular flow in response to loss of functioning nephrons. Moreover, conditioned medium from superfused cells was transferred to cells grown under static conditions in order to test whether PTCs release growth promoting factors under flow.

Results: 

Superfusion of both proximal tubular cell preparations resulted in a flow-dependent cellular hypertrophy since cell volume increased up to 120% and protein / DNA ratio increased up to 150% compared to static cells. Flow-induced increase in cell size was diminished in response to the TGF-b receptor blocker SB421543 (10 mM). Transfer of conditioned medium from superfused cells induced a hypertrophy of PTCs (protein / DNA +23%) while conditioned medium from static cells had no effect. Heating of conditioned medium completely prevented its growth promoting effects.

Conclusion: 

Mechanical stimulation by flow induces hypertrophy of proximal tubular cells. Furthermore, flow stimulates secretion of factors which induce protein synthesis. TGF-b might be involved in the flow-induced increase in cell size.