Fig. 6

Proposed molecular effect of chronic osmotic stress on collagen production. Osmotic stress induces the expression of the profibrotic early growth response factor-1 (Egr-1), which can directly induce the transcription of collagen-III and collagen-IV. Hyperosmolarity also induces profibrotic TGF-ß expression, which can lead to AP-1 activation through cFos and cJun, therefore directly upregulate collagen expression. Egr-1 might also directly activate cJun and promote further AP-1 activation. Moreover, we postulate that TGF-ß and Egr-1 might induce each other in the renal medulla (dotted arrows), enhancing their profibrotic effects