Periostin Attenuates Cyclophosphamide-induced Bladder Injury by Promoting Urothelial Stem Cell Proliferation and Macrophage Polarization.
Periostin Attenuates Cyclophosphamide-induced Bladder Injury by Promoting Urothelial Stem Cell Proliferation and Macrophage Polarization.
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DOI：
10.1093/stcltm/szac025
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发表时间：
2022-06-22
影响因子：
6
通讯作者：
Jiang, Mei Hua
中科院分区：
文献类型：
--
作者：
Chen, Zhihong;Liu, Liyong;Chen, Yunhua;Liu, Minjie;Xiang, Andy Peng;Deng, Chunhua;Jiang, Mei Hua
间质性膀胱炎（IC）是一种病因不明的膀胱综合征，目前尚无普遍接受的治疗方法。越来越多的证据表明，骨膜蛋白（POSTN）是成人组织修复和再生的重要稳态成分，但其在膀胱再生中的功能尚不清楚。在环磷酰胺（CYP）诱导的间质性膀胱炎模型中，我们研究了POSTN是否参与膀胱组织修复。POSTN主要在膀胱间质（逼尿肌平滑肌和固有层）中表达，并在cypp诱导的损伤中表达上调。POSTN缺乏导致更严重的血尿，加重膀胱水肿和延迟伞细胞恢复。此外，在暴露于CYP后的POSTN - / -小鼠中，检测到增殖较少的尿路上皮细胞（由pHH3、Ki67和EdU标记）和较低的Krt14（一种尿路上皮干细胞标记物）表达，表明尿路上皮再生有限。进一步研究发现，POSTN可诱导Wnt4上调并激活AKT信号，两者共同激活β-catenin信号，驱动尿路上皮干细胞增殖。此外，POSTN可以促进常驻巨噬细胞增殖和极化到促再生（M2）表型，这有利于尿路上皮再生。此外，我们制备了可注射的P-GelMA颗粒水凝胶作为生物材料载体，将重组POSTN递送到膀胱中，可以增加尿路上皮干细胞数量，减少伞状细胞脱落，从而减轻cypp诱导的间质性膀胱炎模型中的血尿。总之，我们的研究结果确定了POSTN在膀胱尿路上皮再生中的关键作用，并表明膀胱内生物材料辅助POSTN输送可能是治疗间质性膀胱炎的有效方法。
Interstitial cystitis (IC) is a bladder syndrome of unclear etiology with no generally accepted treatment. 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−/− 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 β-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.
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影响因子：
30.3
作者：
Mysorekar IU;Isaacson-Schmid M;Walker JN;Mills JC;Hultgren SJ
通讯作者：
Hultgren SJ
影响因子：
3.7
作者：
Peyton CC;Burmeister D;Petersen B;Andersson KE;Christ G
通讯作者：
Christ G
影响因子：
6
作者：
Hausmann, Simone;Regel, Ivonne;Erkan, Mert
通讯作者：
Erkan, Mert
DOI：
10.1152/ajprenal.00282.2013
发表时间：
2013-10-01
影响因子：
4.2
作者：
Carattino, Marcelo D.;Prakasam, H. Sandeep;Apodaca, Gerard
通讯作者：
Apodaca, Gerard
DOI：
10.1111/j.1365-2184.1986.tb00725.x
发表时间：
1986-03-01
期刊：
CELL AND TISSUE KINETICS
影响因子：
--
作者：
JOST, SP;POTTEN, CS
通讯作者：
POTTEN, CS