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Growing evidence suggest that periostin (POSTN) is an important homeostatic component in the tissue repair and regeneration in adulthood, but its function in urinary bladder regeneration is still unknown. Here we investigate whether POSTN is involved in bladder tissue repair in a cyclophosphamide (CYP)-induced interstitial cystitis model. POSTN is primarily expressed in bladder stroma (detrusor smooth muscle and lamina propria) and upregulated in response to CYP-induced injury. POSTN deficiency resulted in more severe hematuria, aggravated edema of the bladder, and delayed umbrella cell recovery. Besides, less proliferative urothelial cells (labeled by pHH3, Ki67, and EdU) and lower expression of Krt14 (a urothelial stem cell marker) were detected in POSTN\u2212\/\u2212 mice post CYP exposure, indicating a limited urothelial regeneration. Further investigations revealed that POSTN could induce Wnt4 upregulation and activate AKT signaling, which together activates \u03b2-catenin signaling to drive urothelial stem cell proliferation. In addition, POSTN can promote resident macrophage proliferation and polarization to a pro-regenerative (M2) phenotype, which favors urothelial regeneration. Furthermore, we generated injectable P-GelMA granular hydrogel as a biomaterial carrier to deliver recombinant POSTN into the bladder, which could increase urothelial stem cells number, decrease umbrella cells exfoliation, and hence alleviate hematuria in a CYP-induced interstitial cystitis model. In summary, our findings identify a pivotal role of POSTN in bladder urothelial regeneration and suggest that intravesical biomaterials-assisted POSTN delivery may be an efficacious treatment for interstitial cystitis.<\/jats:p>","DOI":"10.1093\/stcltm\/szac025","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T11:34:08Z","timestamp":1651145648000},"page":"659-673","source":"Crossref","is-referenced-by-count":13,"title":["Periostin Attenuates Cyclophosphamide-induced Bladder Injury by Promoting Urothelial Stem Cell Proliferation and Macrophage Polarization"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9545-1327","authenticated-orcid":false,"given":"Zhihong","family":"Chen","sequence":"first","affiliation":[{"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s Republic of China"},{"name":"Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children\u2019s Hospital, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s Republic of China"},{"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhua","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Tissue Restoration and Reconstruction, School of Materials Science and Engineering, South China University of Technology , Guangzhou, Guangdong , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjie","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Peng Xiang","sequence":"additional","affiliation":[{"name":"Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children\u2019s Hospital, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s Republic of China"},{"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Hua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children\u2019s Hospital, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s Republic of China"},{"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s Republic of China"},{"name":"Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, Guangdong , People\u2019s 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