The acute phase protein haptoglobin is locally expressed in arthritic and oncological tissues

Abstract

Haptoglobin is an acute phase protein known to be highly expressed in the liver. Recently, we showed increased local arterial haptoglobin expression after flow-induced arterial remodelling and found that haptoglobin is involved in cell migration and arterial restructuring probably through accumulation of a temporary gelatin matrix. Since cell migration and matrix turnover are important features in the pathology of arthritis and cancer, we hypothesized that haptoglobin is also locally expressed in arthritic and oncological tissues. In this study, we investigated local haptoglobin expression in arthritic rats (n = 12) using semi-quantitative PCR and Western blotting, and we studied haptoglobin mRNA localization in human kidney tumours (n = 3) using in situ hybridization. The arthritic rats demonstrated an increase of haptoglobin mRNA (2.5-fold, P < 0.001) and protein (2.6-fold, P < 0.001) in the arthritic Achilles tendon. Haptoglobin protein was also increased in the arthritic ankle (2.6-fold, P < 0.001) but not in the non-arthritic knee. In human kidney tumours, tumour and stromal cells produced haptoglobin mRNA. This study shows that the liver protein haptoglobin is, in addition to the artery, also expressed in arthritic and oncological tissues that are recognized for enhanced cell migration and matrix turnover.

Figure 1

Haptoglobin mRNA and protein expression in arthritic rats. (a) Haptoglobin mRNA levels in control and arthritic rats; (b) Western blot analysis of haptoglobin protein in ankle, tendon and knee (c = control rats, a = arthritic rats); (c) haptoglobin protein levels in control and arthritic rats. n = 9, *P < 0.001, black bar = control rats, grey bar = arthritic rats.

Figure 2

In situ hybridization on human kidney tumours using an antisense probe against human haptoglobin mRNA. (a) Haptoglobin mRNA expression by invasive tumour cells (magnification = 100×); (b) in situ hybridization using a sense probe (magnification = 100×); (c) detail of the indicated area in (a) (magnification = 400×); (d) haptoglobin mRNA expression by surrounding stromal cells (magnification = 200×). T = tumour tissue, N = normal kidney tissue, bar = 25 µm.