Collagen prolyl 4-hydroxylation in the skin. Roles in tissue composition, response to injury, and integrin binding.

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Lecture Hall F101, University of Oulu

Topic of the dissertation

Collagen prolyl 4-hydroxylation in the skin. Roles in tissue composition, response to injury, and integrin binding.

Doctoral candidate

Master of Science Kati Drushinin

Faculty and unit

University of Oulu Graduate School, Faculty of Biochemistry and Molecular Medicine, Biochemistry and Molecular Medicine

Subject of study

Biochemistry and Molecular Medicine


Professor Mikko Lammi, University of Umeå


Professor Johanna Myllyharju, University of Oulu

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Collagen prolyl 4-hydroxylation in collagen fibril formation, matrix organization and injury response in mouse skin

In this thesis work we have studied the role of collagen prolyl-4-hydroxylase (P4H) activity in the skin of mice and wound healing, as well as the potential effects of decreased P4H activity on the collagen fibril formation and their biophysical properties.

Collagens are the most abundant proteins in human body and they give support and integrity for all organs and tissues. P4H is the enzyme required to achieve the thermostable triple-helical structure of the collagen molecules. The first mutations identified in humans in the P4H gene lead to a congenital incurable connective tissue disease with changes in tendons, bones, muscles and eyes.

In my dissertation I show with genetically modified mice that decreased P4H activity leads to structural changes in the skin, a decreased amount of collagen in the dermis, a smaller collagen fibril diameter and dilated capillary basement membranes. The observed structural abnormality of the connective tissue in the skin does not change the speed of wound closure but results in a more pronounced inflammatory response resulting from a cutaneous wound or topical chemical irritation.

Cells interact with collagen via certain receptors. One group of receptors is formed by the collagen binding integrins, which bind to collagen fibrils via specific binding sites in the collagen sequence. In this thesis I show that a stable triple-helical collagen structure generated by sufficient P4H activity is a requirement for proper collagen-integrin binding.

This thesis provides new insights into the role of P4H enzyme activity in collagen synthesis, collagen fibril formation, skin structure and function. The thesis work also provides new information on the role of P4H in collagen binding to its integrin receptor and its role in wound healing and activation of inflammatory response.
Last updated: 1.3.2023