RESUMO
Tenascin-C (TNC) is an extracellular matrix protein that is transiently expressed in close association with tissue remodeling in various organs. Expression of TNC in patients with tubulointerstitial nephritis (TIN) is not well-characterized. Using renal biopsy specimens from 25 patients with TIN and 8 patients with thin basement membrane disease (controls), we assessed immunohistochemical staining for TNC and investigated its relation with clinicopathologic data. TNC was undetectable in the controls, but TNC was observed in the interstitium of specimens from all patients with TIN, and strong TNC staining was detected within active tubulitis lesions. TNC was not principally expressed in glomeruli, and it was also absent from scar tissue. Comparison with Sirius red staining revealed that TNC was present where collagen fibers had not yet formed. The percent area of TNC within the interstitium (% TNC-positive area) showed a significant negative correlation with illness duration and significant positive correlations with the serum CRP level and eGFR aggravation, both of which reflect disease activity. On the other hand, no correlation was found between % TNC-positive area and eGFR recovery during 2 years of follow up. Examination of renal biopsy specimens from TIN patients revealed that TNC appears during the active stage of inflammation and then disappears with healing. This suggests that TNC expression reflects TIN disease activity, but not prognosis.
RESUMO
Prorenin receptor (PRR) has been implicated in the onset and progression of various renal diseases, though its possible association with immunoglobulin A (IgA) nephropathy remains unclear. In the present study, we tried to clarify expression and pathophysiological significance of PRR in IgA nephropathy. We immunohistochemically assessed PRR levels in renal biopsy specimens from 48 patients with IgA nephropathy and evaluated its relevance to the clinical and pathological features of the disease. PRR was detected mainly in renal tubular cells, which was confirmed at the subcellular level using immunoelectron microscopy. The PRR-positive area (%PRR area) correlated with daily urinary protein, which is known to reflect disease severity (r=0.286, P=0.049). PRR levels were weaker in tubular cells bordering areas of severe interstitial fibrosis, where α-smooth muscle actin-positive myofibroblasts were present. We also used immunohistochemical detection of microtubule-associated protein-1 light chain 3 (LC3) and electron microscopy to assess autophagy, a cytoprotective mechanism downstream of PRR. We noted an apparent coincidence between autophagy activation in tubular cells and PRR expression in the same cells. Taken together, our findings suggest that renal expression of PRR in IgA nephropathy may be a compensatory response slowing disease progression by preventing tubular cell death and subsequent fibrosis through activation of cytoprotective autophagic machinery. Further studies using different type of kidney diseases could draw conclusion if the present finding is a generalized observation beyond IgA nephropathy.