Renal lymph circulation blockage alters the epithelial cell phenotype and tubular integrity: role of distinct regulation of BMP7 and TGF-β/Smads signaling pathway.

AIMS

To investigate the effect of lymph circulation blockage on the alteration of renal epithelial cell phenotype and the tubular integrity, as well as the underlying mechanisms.

METHODS

Wistar rats received left renal lymph ligation and right renal nephrectomy (KL group) or right renal nephrectomy without lymph ligation (KN group) and then were killed on day 14, day 28 and day 56. The urine, blood and kidney tissue were collected for the analysis of protein and gene expressions and morphological changes.

RESULTS

The urine albumin and serum creatinine (Cr) in KL group were significantly increased compared with KN group. Masson and PAS staining indicated the epithelial cell degeneration, necrosis, sublethal loss and atrophy in KL rats, but not in KN group. Interestingly, from the atrophic tubules, some epithelial cells exhibited polarity changes with hypertrophy contrasting to the normal epithelial morphology of KN group throughout the experiment. By EM, ligated kidneys showed irregularly wrinkled basement membranes and epithelial cell swelling. Some intertubular areas of the KL kidney were expanded with fibrotic matrix and fibroblast-like cells. In line with these morphological changes, the fibroblast cell markers of FSP1 and α-SMA were markedly increased in contrast to the remarkable reduction in epithelial cell marker E-cadherin and tight junction protein ZO-1. Moreover, the TGF-β1/Smad2/3 signaling pathway was significantly activated in KL rats in contrast to a robust downregulation of BMP7/Smad5 signaling.

CONCLUSIONS

Disturbance of renal lymphatic circulation resulted in the epithelial cell phenotypic alteration and impaired tubular integrity possibly via distinct regulation of TGFβ1/Smads and BMP7/Smad5 signaling pathway.