Expression Profile of Hyaluronidase mRNA Transcripts in the Kidney and in Renal Cells

Abstract

The accumulation of hyaluronan (HA) in the renal cortex is a characteristic feature of inflammatory renal diseases. Fragments of HA derived from high molecular weight precursors are known to display inflammatory effects in vitro and could, therefore, participate in immune renal injury. To understand the mechanisms of HA fragmentation in vivo we examined the expression of recently characterized mammalian hyaluronidases in normal and autoimmune kidneys and in cell lines. We found that transcripts for the lysosomal–type hyaluronidases Hyal1 and Hyal2 were constitutively expressed in normal and autoimmune kidneys as well as in tubular epithelial cells and in a macrophage cell line. The expression of hyaluronidase genes in the cell lines did not increase in response to treatment with tumor necrosis factor alpha or gamma interferon. Interestingly, transcripts for the testicular–type hyaluronidase PH–20 (Spam1, Hyal3) were also detected in normal and autoimmune kidneys as well as in tubular cells and macrophages. Transcript levels were higher in kidneys from male mice as compared with age–matched females. Again, transcript levels did not change in vitro in response to cytokines. We conclude that mRNA for three different hyaluronidases is found in murine kidneys. The functional role played by these hyaluronidases in the degradation and metabolism of HA remains to be investigated further.

Hydrogel-embedded endothelial progenitor cells evade LPS and mitigate endotoxemia

“…Two days later, mice received intraperitoneal injection of LPS, followed by release of HA hydrogel-embedded EPCs. [The release of subcapsularly implanted EPCs occurs due to the constitutive activity of hyaluronidase in the kidney, thus negating the need for exogenous hyaluronidase (8,16,18,19,32).] Plasma creatinine levels were significantly elevated in LPS-treated animals (Fig.…”

“…When HA hydrogels are implanted subcapsularly, the locally enhanced activity of these enzymes is sufficient to digest the scaffold and release the cells (16,28). Some of the highly desirable therapeutic advantages of delivering cells embedded in HA hydrogel consist in 1) the ability to externally time their release and, even more remarkable, 2) the intrinsic capacity of the injured organ to regulate the release of EPCs from the implanted scaffold (organs such as the kidney constitutively release endogenous hyaluronidase) (8,16,18,19,32). The duration of a latent period before cells are released from the scaffold and become exposed to the circulating cytotoxins represents the major difference between the adoptive transfer of cells via hydrogel vs. intravenous delivery.…”

“…For kidney implantation, mice were anesthetized as above, kidneys were exposed by a midline incision, and 10 l of HA hydrogel loaded with fluorescently labeled (CellTracker CM-DiI) EPCs (5 ϫ 10 5 cells each side or 38 ϫ 10 6 per kg of body wt) were injected under the renal capsule of both kidneys. Kidney gel implants were not subsequently digested with collagenase/ hyaluronidase enzymes due to their endogenous production by kidneys (8,16,18,19,32). After recovery from gel implantation procedures, LPS was injected intraperitoneally (3.5 mg/kg) or CLP was performed to induce sepsis.…”

Xenopus kidney hyaluronidase‐1 (XKH1), a novel type of membrane‐bound hyaluronidase solely degrades hyaluronan at neutral pH1

“…Taken together, XKH1 is a novel type of HA-degrading enzyme that clearly di¡ers from the sperm hyaluronidase PH-20 by several characteristic aspects. Though it is not the functional homolog of mammalian PH-20 with respect to fertilization, its expression in the kidney is reminiscent of that of PH-20 in this organ [15]. Furthermore, at the genomic level, we cannot rule out that XKH1 and PH-20 originate from a common ancestor and thus, have to be considered structural homologs.…”

Evidence That the Serum Inhibitor of Hyaluronidase May Be a Member of the Inter-α-inhibitor Family

“…Expression is also detectable in fetal and placental cDNA libraries by polymerase chain reaction, suggesting a possible role for this gene during embryonic development (19). Some RNA can also be detected in kidney and prostate libraries (65), although no protein can be detected. We have confirmed these results.…”