開發尋找慢性腎臟病潛在治療標的之策略

Abstract

慢性腎臟病(CKD)是世界上最迫切且尚未解決的健康問題之一。它也成為亞洲許多人的夢魘，尤其是俗稱「腎臟透析王國」的台灣。目前慢性腎臟病的治療方法有血液透析、腹膜透析、藥物治療等。這些治療方法僅能幫助減輕不適或延緩病程，然而，它們卻無法完全遏止慢性腎臟病的進展。因此，確定慢性腎臟病新的治療標靶是必要的，並且可視為前景廣闊。本文的研究目的是確定慢性腎臟病的新治療標靶。首先，我們進行了文獻綜述，以尋找可能成為慢性腎臟病新標靶的候選基因。接下來，我們使用GEO資料庫評估了這些基因在健康和纖維化腎臟上的基因表現量。我們發現NCK Adaptor Protein 2 (NCK2)，酪胺酸激酶(NCK)家族非催化區的成員之一，在纖維化腎臟中高表達，指示它有可能成為慢性腎臟病的新標靶。經過實驗驗證，結果推測NCK2的過度表現會輕微抑制人類近端腎小管細胞(HK-2)的細胞活力。這項觀察結果可能會導致未來更進一步的機制研究和藥物開發，並嘗試為慢性腎臟病患者提供全新的治療選擇。透過這項結果，人們可以預期改善慢性腎臟病患者的健康和生活品質。

Chronic kidney disease (CKD) is one of the most urgent and unresolved health issues in the world. It has also been a plague for many people in Asia, especially Taiwan, commonly referred to as the "Kingdom of Kidney Dialysis." CKD is now treated with hemodialysis, peritoneal dialysis, medication management. These therapies can only help to lessen discomfort or delay the course of the illness; they cannot, however, halt CKD progression. Thus, identification of new therapeutic targets for CKD will be required and promising. The aim of the study is to identify new intervention targets for CKD treatment. First, we performed a literature review to identify candidate genes that potentially could be new therapeutic targets of CKD. Next, we evaluated gene expression levels of these genes on healthy and fibrotic kidneys by using the GEO database. We found that NCK adaptor protein 2 (NCK2), a member of the Non-catalytic region of tyrosine kinase (NCK) family, was highly expressed in the fibrotic kidneys, suggesting it could be a new therapeutic target for CKD. After the experimental verification, the result speculated that overexpression of NCK2 slightly inhibited the viability of human proximal tubular cells (HK-2). This observation may lead to future mechanistic study and drug development and an attempt to give novel treatment options for patients with CKD. With this outcome, people can anticipate to improve the health and quality of life of those who suffer from CKD.