Hyaluronan turnover in hyaluronidase 3- and β-hexosaminidase-deficient mice
Bibliographic record
Abstract
Hyaluronan (HA) is a glycosaminoglycan that is abundant in the extracellular matrix of vertebrate cells. Under physiological conditions HA exists in a high-molecular-weight form, whereas HA fragments accumulate at sites of tissue injury and inflammation. Hyaluronidases are a group of enzymes that initiate the breakdown of HA. In humans, six hyaluronidase-like sequences have been identified in two locations, 3p21.3 (HYAL1, HYAL2 and HYAL3) and 7q31.3 (HYAL4, SPAM1 and HYALP1). Deficiency of one of these enzymes, HYAL1, was identified in a patient with Mucopolysaccharidosis IX, a disorder characterized by peri-articular soft masses containing HA-filled lysosomes. Given the broad distribution of HA and the mild phenotype of the patient, it is likely that other hyaluronidases or possibly the exoglycosidases, β-hexosaminidase and β-glucuronidase, are playing a major role in HA degradation. To address the potential role of HYAL3 in HA degradation in health and disease, a Hyal3-deficient mouse model was generated. Hyal3-deficient mice were viable, fertile and appeared to have no gross phenotype. The only difference observed was a subtle change in the cellularity and tissue structure of lungs from aged Hyal3-deficient mice. Further studies focused on analysis of HA homeostasis revealed a significant increase in HA in the airways of Hyal3-deficient lungs. Altered HA homeostasis is observed in rodent models of several lung conditions. In order to further study the role of Hyal3 in lungs, an ovalbumin-challenged inflammation model was generated in Hyal3-deficient mice. A significant increase in lung HA levels and altered distribution of HA in the airways of lungs was detected in ovalbumin-challenged Hyal3-deficient mice. Moreover, lung inflammation and airway resistance were increased in Hyal3-deficient mice after ovalbumin-challenge compared to similarly treated Hyal3-control mice. This suggests HA homeostasis that is altered during Hyal3-deficiency might be directly or indirectly promoting inflammation and airway resistance. Because the reported level of HA accumulation was very low in Hyal1-deficient and Hyal2-deficient mice, and in our studies of Hyal3-deficient mice, we performed preliminary studies to assess a role for an exoglycosidase, β-hexosaminidase, in HA turnover. Our preliminary studies indicate there is no or little HA accumulation in β-hexosaminidase-deficient mouse tissues. To conclude, our study of Hyal3- and β-hexosaminidase-deficient mice suggests that these are not the major enzymes involved in HA degradation
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".